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

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

Oncology Emergencies in the PICU 1- TUMOR LYSIS SYNDROME 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.

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

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

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

TUMOR LYSIS SYNDROME 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

TUMOR LYSIS SYNDROME MANAGEMENT: cont. Urine analysis and pH HYDRATION THERAPY: 2-3 L/m2/day OR 1 1/2 to 2 x maintenance Start 24-48 hrs prior to chemotherapy. Isotonic NS or Hypotonic saline if Urine Na <150 meq/L Alkalinization of the urine to pH = 6-7 controversial ! Diuretics controversial ! Mannitol if suboptimal diuresis Avoid P.O. or exogenous K+, potassium sparing diuretics, ACE inhibitors and uric acid tubular re-absorption blockers.

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

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

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

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

TUMOR LYSIS SYNDROME 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 Costs C.I. in G6PD deficiency ====================

Oncologic Emergencies in PICU 2- Hyperleukocytosis WBC counts > 100,000/ul in 5-20% children ALL Clinically significant if > 300,000 in ALL Marked elevation of blood viscosity: erythrocyte + Leukocyte volumes and deformability of cells. Normal = 1.5 relative to water Clinical manifestation if > 4 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 !!

Hyperleukocytosis 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. Exchange transfusion & Leukapheresis; Needs anticoagulants and vascular access. Rebound WBC count. No effect on pulmonary status, CNS outcome or mortality. NO ROLE FOR STEROIDS NOR emergency CRANIAL RADIATION

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!!

Anterior Mediastinal Mass Lymphomas Teratomas Middle: Lymphoma Posterior: neuroblastoma

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

Anterior Mediastinal Mass 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

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

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

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.

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. Three needed chemotherapy or radiation prior to extubation. However all survived. Ferrari et al; General Anesthesia prior to treatment of anterior mediastinal masses in Pediatric cancer patients, Anesthesiology 1990

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

Oncology emergencies in the PICU 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. Everyone has an important role in the team, BUT there must be a “Captain of the Ship”.

NOW Back to our patient