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

Oncology EmergenciesOncology Emergenciesin PICUin PICU

Norah Khathlan MDNorah Khathlan MDPediatric IntensivistPediatric Intensivist

Director PICUDirector PICUNovember 2006November 2006

Oncology Emergencies in the Oncology Emergencies in the PICUPICU

• MEDIASTINAL MASSES MEDIASTINAL MASSES

• SVC SyndromeSVC Syndrome

• HYPERLEUKOCYTOSISHYPERLEUKOCYTOSIS

• TUMOR LYSIS SYNDROMETUMOR LYSIS SYNDROME

• SEPTIC SHOCKSEPTIC SHOCK

• ARDSARDS

• SPINAL Cord Compression.SPINAL Cord Compression.

• CNS EventsCNS Events


1- TUMOR LYSIS SYNDROME1- TUMOR LYSIS SYNDROME

• Metabolic abnormalities occurring as a Metabolic abnormalities occurring as a result of tumor cell death:result of tumor cell death:– SpontaneouslySpontaneously– ChemotherapyChemotherapy

• Starting chemotherapy on rapidly growing-Starting chemotherapy on rapidly growing-chemo-sensitive tumors chemo-sensitive tumors release of release of intracellular contents into circulation.intracellular contents into circulation.

TUMOR LYSIS SYNDROMETUMOR LYSIS SYNDROME

• Hyperkalemia.Hyperkalemia.

• Hyperphospatemia.Hyperphospatemia.

• 22ryry Hypocalcemia. Hypocalcemia.

• Hyperuricemia.Hyperuricemia.

• Uremia.Uremia.

• High creatinine.High creatinine.

• Oliguria.Oliguria.


• Incidence:Incidence:– 70% of hematological malignancies 70% of hematological malignancies laboratory laboratory

criteria of TLS.criteria of TLS.– 3% with clinical TLS. 3% with clinical TLS.

• Associated with hematological malignancies:Associated with hematological malignancies:– ALLALL– AMLAML– LymphomasLymphomas– Solid tumorsSolid tumors


• Maybe precipitated by :Maybe precipitated by :– ChemotherapyChemotherapy– steroidssteroids– Radiotherapy.Radiotherapy.– Hormonal agents.Hormonal agents.

• Risk factors:Risk factors:– Tumor typeTumor type– DehydrationDehydration– Preexisting renal insufficiencyPreexisting renal insufficiency– Nephrotoxic medicationsNephrotoxic medications

• High LDH in TLS is indicative of likely progression High LDH in TLS is indicative of likely progression to ARFto ARF


• MANAGEMENT:MANAGEMENT:– Identify at risk patients.Identify at risk patients.– Admit to PICU.Admit to PICU.– Consult Nephrology serviceConsult Nephrology service– Establish good venous access Establish good venous access prefer.prefer. CVC. CVC.– Frequent lab monitoring of:Frequent lab monitoring of:

- Na- Na++ - Ca- Ca++++

- K- K++ - Uric acid- Uric acid- Cl- Cl-- - Creatinine- Creatinine- PO4- PO4++++ - Urea- Urea- Bicarbonate- Bicarbonate - LDH- LDH


• MANAGEMENT: MANAGEMENT: cont.cont.

– Urine analysis and pHUrine analysis and pH– HYDRATION THERAPY:HYDRATION THERAPY:

• 2-3 L/m2-3 L/m22/day OR 1 1/2 to 2 x maintenance/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/LIsotonic NS or Hypotonic saline if Urine Na <150 meq/L• Alkalinization of the urine to pH = 6-7 Alkalinization of the urine to pH = 6-7 controversialcontroversial ! !• Diuretics Diuretics controversialcontroversial ! !• Mannitol if suboptimal diuresisMannitol if suboptimal diuresis• Avoid P.O. or exogenous KAvoid P.O. or exogenous K++, potassium sparing , potassium sparing

diuretics, ACE inhibitors and uric acid tubular re-diuretics, ACE inhibitors and uric acid tubular re-absorption blockers.absorption blockers.


• Specific management:Specific management:– Hyperkalemia:Hyperkalemia:

– Ca gluoconateCa gluoconate– Na BicarbonateNa Bicarbonate– Insulin & GlucoseInsulin & Glucose– SalbutamolSalbutamol– K binding resinsK binding resins

– DIALYSIS or CRRT “CVVHD” for K>5DIALYSIS or CRRT “CVVHD” for K>5


• Hyperphosphatemia & 2ry Hyperphosphatemia & 2ry Hypocalcemia:Hypocalcemia:– Phosphate binders eg. Aluminum Phosphate binders eg. Aluminum

antacids.antacids.– Avoid unnecessary Ca supplements.Avoid unnecessary Ca supplements.– PO4 > 4 is an indication for dialysis.PO4 > 4 is an indication for dialysis.– Consider CRRT.Consider CRRT.


• Hyperuricemia:Hyperuricemia:

•Urine Alkalinization maximizes Uric acid Urine Alkalinization maximizes Uric acid solubilitysolubility

•Urine pH > 6 and < 7.5Urine pH > 6 and < 7.5

•Avoid urine pH more than 7.5 Avoid urine pH more than 7.5 ““may lead to may lead to massive phosphate crystalluria and phosphate precipitates”.massive phosphate crystalluria and phosphate precipitates”.

Tumor Lysis SyndromeTumor Lysis Syndrome

• Allopurinol:Allopurinol:– Xanthine oxidase inhibitor:Xanthine oxidase inhibitor:

Xanthine HypoxanthineXanthine Hypoxanthine XXanthine oxidae -anthine oxidae -

-ve -ve allopurinolallopurinol

Uric AcidUric Acid

– Blocks production of Blocks production of newnew Uric acid Uric acid– Increased levels of uric acid precursors; XanthineIncreased levels of uric acid precursors; Xanthine

nephrotoxicnephrotoxic– Impairs chemotherapy metabolismImpairs chemotherapy metabolism


• Hyperuricemia: cont.Hyperuricemia: cont.– Non recombinant urate oxidase (Uricozyme)Non recombinant urate oxidase (Uricozyme)

urate oxidaseurate oxidase

Uric AcidUric Acid -------------------------- -------------------------- Allantoins Allantoins “highly soluble “highly soluble in urine”in urine”

– Recombinant Urate Oxidase (Rasburicase)Recombinant Urate Oxidase (Rasburicase)• Effective: Single dose decreases uric acid from 15 to Effective: Single dose decreases uric acid from 15 to

0.4 mg/dl in 24 hrs 0.4 mg/dl in 24 hrs • Costs Costs • C.I. in G6PD deficiencyC.I. in G6PD deficiency

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Oncologic Emergencies in Oncologic Emergencies in PICUPICU

2- Hyperleukocytosis2- Hyperleukocytosis

• WBC counts > 100,000/ul in 5-20% children ALLWBC 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 waterNormal = 1.5 relative to water• Clinical manifestation if > 4Clinical manifestation if > 4• Mainly affects CNS & LungsMainly affects CNS & Lungs

– Leukocyte aggregation.Leukocyte aggregation.– Small vessel obstruction.Small vessel obstruction.– Decreased perfusion of microcirculation.Decreased perfusion of microcirculation.– Vascular stasis, Leukostasis.Vascular stasis, Leukostasis.– Risk of Intra Cranial Hmg and /or IVH & SAHRisk of Intra Cranial Hmg and /or IVH & SAH– Role of Cytokines !!Role of Cytokines !!

HyperleukocytosisHyperleukocytosis

• ManagementManagement::– Lack of controlled trials.Lack of controlled trials.– Avoid Packed RBCs transfusionAvoid Packed RBCs transfusion– Avoid diuretics.Avoid diuretics.– Maintain platelets > 20,000Maintain platelets > 20,000– Correct coagulopathyCorrect coagulopathy– Hydration,? Alkalinization and allopurinol:Hydration,? Alkalinization and allopurinol:

• Used in ALL & WBCs > 100,000 Used in ALL & WBCs > 100,000 80% reduction in 36hrs no complications. 80% reduction in 36hrs no complications.

– Exchange transfusion & Leukapheresis;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 NO ROLE FOR STEROIDS NORNOR emergency CRANIAL RADIATION emergency CRANIAL RADIATION


3- Anterior Mediastinal Mass3- Anterior Mediastinal Mass

Airway & circulatory compromise posed Airway & circulatory compromise posed by mediastinal masses provide some by mediastinal masses provide some of the great challenges in the PICU of the great challenges in the PICU

and in ORand in OR

This is a genuine emergency!!This is a genuine emergency!!

Anterior Mediastinal MassAnterior Mediastinal Mass

• Anterior:Anterior:– LymphomasLymphomas– TeratomasTeratomas

• Middle:Middle:– LymphomaLymphoma

• Posterior:Posterior:– neuroblastomaneuroblastoma


• Signs & Symptoms:Signs & Symptoms:– Respiratory symptoms predominate: Respiratory symptoms predominate: > 50% > 50%

narrowingnarrowing• Air hungerAir hunger• DyspneaDyspnea• WheezingWheezing• AnxietyAnxiety• Position of comfort.Position of comfort.

– SVC obstruction symptoms:SVC obstruction symptoms:• Facial swellingFacial swelling• Periorbital edemaPeriorbital edema• Conjunctival suffusionConjunctival suffusion• Headache & Dizziness Headache & Dizziness


• Evaluation:Evaluation:– Quick & cautious approach is a must!!!Quick & cautious approach is a must!!!– Inappropriate delay, investigation and /or Inappropriate delay, investigation and /or

management may be management may be catastrophic !!catastrophic !!

•CXR: PA & Lat. wide mediastinum•CT Chest:

– No sedation May lead to cardio-

respiratory arrest– No supine position


• CBC & blood filmCBC & blood film

• LDHLDH

• ΒΒ-HCG & -HCG & αα-fetoprotein-fetoprotein

• BMA & biopsyBMA & biopsy

• Pleural fluid LOCAL Pleural fluid LOCAL AnestheticAnesthetic

• Pericardial fluid OnlyPericardial fluid Only

• Lymph node biopsyLymph node biopsy


If still no diagnosis:If still no diagnosis: nearly 27% of cases nearly 27% of cases

Empiric therapyEmpiric therapy– SteroidsSteroids– ChemotherapyChemotherapy– RadiationRadiation

OROR

More Invasive testingMore Invasive testing


Accurate diagnosis is preferable but Accurate diagnosis is preferable but Significant risk of induction of general Significant risk of induction of general

anesthesia must be consideredanesthesia must be consideredPredictors of safe G.A.:Predictors of safe G.A.:– Echo to evaluate cardiac motility & venous returnEcho to evaluate cardiac motility & venous return– PFT : PEF rates > 5o% predictedPFT : PEF rates > 5o% predicted– Tracheal cross-sectional area > 50% Tracheal cross-sectional area > 50%

• Different Protocols for different PICUs Different Protocols for different PICUs depending on the available support.depending on the available support.


In a Study to assess risk of G.A in patients In a Study to assess risk of G.A in patients with SVC syndrome,163 children with with SVC syndrome,163 children with anterior mediastinal masses were anterior mediastinal masses were reviewed:reviewed:– 44 underwent G.A. prior to therapy: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 Three needed chemotherapy or radiation prior to

extubation.extubation.• However all survived.However all survived.

• Ferrari et al; General Anesthesia prior to treatment of anterior mediastinal Ferrari et al; General Anesthesia prior to treatment of anterior mediastinal masses in Pediatric cancer patients, Anesthesiology 1990masses in Pediatric cancer patients, Anesthesiology 1990


• Intubation should be performed:Intubation should be performed:– Awake with FOB.Awake with FOB.– Spontaneously breathing.Spontaneously breathing.– Sitting position.Sitting position.– Lower extremities venous access.Lower extremities venous access.– Standby ECMO or CPBStandby ECMO or CPB

• If above is not feasible:If above is not feasible:

Seriously consider empiric steroids +/- chemo or Seriously consider empiric steroids +/- chemo or radiotherapyradiotherapy

Oncology emergencies in the Oncology emergencies in the PICUPICU

• Coordination of care is essential for optimal care.Coordination of care is essential for optimal care.

• Communication and collaboration among the Communication and collaboration among the members of the health care team improves members of the health care team improves quality and efficiency of patient care.quality and efficiency of patient care.

• Everyone has an important role in the team, Everyone has an important role in the team, BUTBUT there must be a there must be a “Captain of the Ship”.“Captain of the Ship”.

NOW Back to our NOW Back to our patientpatient

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

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