Emergencies in Pediatric Oncology

Katarzyna Muszynska-Roslan

Department of Pediatric Oncology and Hematology Medical University of Bialystok

Pediatric oncologic Emergencies

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Pediatric oncologic Emergencies

4 major types

Metabolic emergencies (hypercalcemia,

hyponatremia, hypoglycemia, adrenal failure, lactic acidosis)

Hematologic emergencies (hyperleukocytosis, DIC, thrombosis, bleeding)

Infectious / Inflammatory emergencies(enetrocolitis, pancreatitis, hemorrhagic cystitis , sepsis)

Mechanical emergencies (cerebral herniation/status epilepticus, cardiac tamponade, SVC syndrome, spinal cord compression )

Objectives

Tumor lysis syndrome

Hyperleukocytosis

Mediastinal masses/superior vena cava syndrome

Spinal cord compression

CNS events

SIADH

VOD

Infections

Tumor Lysis Syndrome - who gets it?

Tumor Lysis Syndrome - who gets it?

Patients with rapidly growing tumors and/or bulky disease

Most common with Burkitt’s lymphoma,

T-cell leukemia/lymphoma, B-cell leukemia

Tumor Lysis Syndrome

Can occur at diagnosis, but more common early after start of chemotherapy

Pathogenesis of TLS

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Pathogenesis of TLS

Rapid death of tumor cells > cells breakdown releaseof large amounts of metabolities (potasssium, phosphate, nucleic acids, urate and other purinemetabolities) into extracellular space

impaired excretion by the kidneys (uric acid is

relatively insoluble, especially at low pH and mayprecipitate in concentrated urine)

urate accumulation

acute renal failure + electrolyte imbalance

Biochemical and clinical consequences of tumor lysis

syndrome

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Biochemical and clinical consequences of tumor lysis

syndromeHyperkalemia weakness, arrhythmia

Hyperphosphatemia hypocalcemia

Hyperuricemia “uric acid nephropathy”

Hypocalcemia tetany, mental status changes, seizures

Renal failure

“The best treatment is prevention”

It is directed at maximizing the excretion of releasedintracelluar contents and minimizing the production of uricacid

Fluid intake = 2-3 L/m2/day

enhances uric acid excretion, phosphate excretion

Exact fluid balance (fluid intake = urine output)

limitation of potassium and phosphate intake

“The best treatment is prevention”

Urine alkalinization – iv. administration of sodium bicarbonate

Uric acid more soluble at urine pH = 7.0 vs 5.0

Goal of urine specific gravity 1.015 and pH

7.0 - 7.5

Caution! - hypoxanthine and Ca-PO4 stones possible if urine pH > 7.5

Allopurinol –

Decrease production of uric acid

competitive inhibitor of xanthine oxidase which decreases conversion of purine metabolites to uric acid

Recombinant Urate oxidase

Decrease production of uric acid, promotes catabolism of uric acid

Catalyzes conversion of uric acid to allantoin

Allantoin more soluble, easily excreted by kidneys

Urine alkalinization unnecessary if used

Observations

Blood tests every 6 - 8 h: Blood gases Complete blood count Sodium, potassium, calcium, magnesium, phosphorus Urea, creatinine, uric acid

Vital signs (pulse, blood pressure, respiratory rate, temperature), Twice daily weight, diuresis, evidence of oedema, signs of electrolyte

abnormality, ECG

Dialysis

Clinical Indications for Dialysis

oliguria, anuria,

volume overload

weakness,

severe cardiac rhythm abnormalities,

seizures,

Biochemical Indications for Hemodialysis

Pathogenesis of ARF in pediatric oncology

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Pathogenesis of ARF in pediatric oncology

Hyperleukocytosis

5-20% of children with new Dx of leukemia have WBC count >100,000/mm3

These patients are at risk of severe complications

from hyperviscosity of blood

Hyperleukocytosis

Blasts interact with endothelium to form aggregates, thrombi in microcirculation

Most problems in CNS, pulmonary and renal circulation

More common with AML than ALL

Myeloblasts and monoblasts larger, less deformible, “stickier”

Pulmonary leukostasis

Pulmonary arteriole with leukostatic thrombus in patient with AML and hyperleukocytosis

Pulmonary leukostasis

Sx: dyspnea, tachypnea, hypoxemia, acidosis,

CXR: diffuse interstitial infiltrates

Problems with gas exchange

Acute respiratory failure

CNS leukostasis

Headache, mental status changes, seizures, coma in spectrum of Sx

blurred vision, confusion, delirium, papilledema

High risk of intracranial hemorrhage and/or thrombosis, especially with AML and thrombocytopenia

Genitourinary leukostasis

Clinical features:

oliguria, anuria,

priapism

Hyperleukocytosis

Diagnosis:

WBC

CNS CT: hemorrhage, leukemic plaques

Chest radiograph/ CT: pneumonitis, leukemic emboli

Therapy for symptomatic hyperleukocytosis

To decrease blood viscosity (directly related to morbidity)

Induction chemotherapy

Carefull hydration

AVOID use of diuretics

AVOID RBC transfusion

(Hb goal < 10 gm/dL for viscosity)

Urine alkalinization, adequate hydratation as with tumor lysis syndrome

Consider leukapheresis

PICU - supportive care - mechanical ventilation, hemodynamic support, etc

Apheresis: a process in which blood of

a patient is passed through a medical device, which separates one or more components of blood

Mediastinal masses

Most common types of mediastinal tumors in children

Anterior

Non-Hodgkin’s lymphoma

Hodgkin’s disease

Teratoma

Middle

Lymphoma

Posterior

Neuroblastoma

Pathophysiology of SVCS or SMS

Displacement or obstruction of:

Tracheobronchial tree

Heart and great vessels

SVCS

Superior mediastinal syndrome

SVC syndrome - plethora, oedema of face & upper extremities; dilatation of veins in area

Presentation and symptoms

Often a subacute hx of cough, low-grade fever, dyspnea, ± orthopnea, ± weight loss

Signs/symptoms of airway obstruction and/or SVC syndrome demand emergency evaluation

Airway obstruction - stridor, dyspnea, anxiety, “position of comfort”

Diagnosis:

Chest radiograph – anterior mediastinal mass

Chest CT – mediastinal mass and compression of trachea and bronchi,

Tissue diagnosis e.g. lymph node biopsy, bone marrow aspiration, pleurocentesis, thoracocentesis

Hist-pat examination

Diagnosis:

Blood tests:

blood gas analysis,

complete blood count with differential

sodium, potassium, calcium, magnesium,

urea, creatinine,phosphorus, uric acid,

lactate dehydrogenase (LDH)

Evaluation – problems…

Inability to tolerate supine position !!!

May result from weight of tumor compressing not only airway, but great vessels and heart (especially RV outflow tract)

If can tolerate anesthesia should be performed biopsy

Evaluation of the child with mediastinal mass

Management/diagnostic decisions difficult and controversial –

emergency treatment vs definitive Dx

Significant stridor, dyspnea usually not present unless airway cross-sectional area narrowed by >50%

CT Scan of Mediastinal Mass Showing Tracheal Compression at Carina

Carina

Mass

Emergent Management

Keep child in sitting, left lateral decubitus position - -helps “lift” mass off airway and RVOT

IV access (lower extremities preferable due to SVC obstruction)

Face mask O2, non-invasive PEEP

Heli-ox possibly helpful due to large airway obstruction decreases airway resistance

Therapy

Urgent radiotherapy since most lymphomas are radiosensitive. (-)

Chemotherapy, including steroids or cyclophosphamide, is a possible alternative to irradiation, especially in children.

Spinal cord compression

Occurs in 3-5% of children with cancer, often at diagnosis.

Can occur with any tumor type, but mostly with neuroblastoma, sarcoma, leukemia, lymphoma, medulloblastoma.

Presentation

Back Pain !:

suspect cord compression when . . . pain not relieved in supine position or back pain has a radicular component!!!

Weakness, sensory abnormalities, and paresis

Paraplegia and quadriplegia can occur rapidly !!@

Urinary and fecal incontinence.

Diagnosis

MRI is the imaging procedure of choice

Treatment

Sx of cord dysfunction:

give dexamethasone bolus of 1-2 mg/kg and obtain MRI

Decompression: surgery, radiation, chemotherapy.

Surgery indicated if tumor type is not known or symptoms progress despite management

Chemotherapy is appropriate for patients with spinal cord compression due to lymphoma, leukemia, and neuroblastoma.

Emergencies related to brain tumors

Hemorrhage:

ICP, Altered consciousness.

Peri-tumor brain edema:

Rx: dexamethasone ± furosemide

Hydrocephalus:

occurs mostly with posterior fossa and midline supratentorial tumors

Rx: urgent CSF shunting

Sepsis in Pediatric Cancer Patients

diagnostic criteria:

Fever/hypothermia

Tachycardia

Tachypnea

Hypoperfusion

Acidosis

Hypotension

Common etiologies:

Gram (+) cocci

-hemolytic Strep

Staph. Epi

Staph aureus

Gram (-) rodsPseudomonas

Enterobacter

E. coli

Fungi

Viruses

Therapy for Sepsis in Pediatric CancerPatients

Empiric broad-spectrum Abx

Early consideration of antifungals

Usual PICU supportive care is nedeed:

Mechanical vent.

Fluids/inotropes

Parenteral nutrition/blood products, etc

Consider aggravated cardiac dysfunction if hx of high-dose anthracyclines, radiation

Beware risk of adrenal suppression in pts with steroid Rx hx

Granulocyte transfusion reportedly helpful in fungal/bacterial sepsis

Ig substitution

Pulmonary infections in childhood cancers - etiology

Bacteria:

-hemolytic Strept.

Staph. Aureus

Pseudomonas

Klebsiella

E coli

others

Pneumocystis carinii

Mycoplasma pneumonia

Fungi: Aspergillus and Candida

Viruses: CMV, herpes simplex, varicella-zoster virus, adenovirus

Risk factors for acute lung injury

Multiple blood products transfusion

Radiation

Sepsis

Amphotericin B

SIRS (systemic inflammatory response syndrom) from other causes(treatment agents, pancreatitis, etc)

Hepatic sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) is a life-threatening complication of HCT - identified as transplant-related, systemic endothelial diseases.

Veno-occlusive disease

Syndrome of Inappropriate Antidiuretic Hormone (SIADH) and Abnormal Sodium Metabolism

Serum sodium level below 120mmol/l

Etiology in pediatric oncology:

The use of vincristine or cyclophosphamide

after CNS irradiation

Pathophysiology of SIADH:

???

Pathophysiology:

Continuous release of ADH without any relation to plasma osmolality

→ the kidneys conserve water and concentrate the urine

→ hyponatremia and water intoxication

Symptoms:

Fatigue

Weight gain

Lethargy, confusion, seizures, coma

Diagnosis:

Urine /plasma osmolality

Serum sodium level

Treatment

Fluid restriction !!!

In case of seizures or coma:

Hydratation with hypertonic saline

200ml/m2 1.5%NaCl - 6 -8h,

than more slowly to normal level- 24 -72h

Diuresis – furosemide 1mg/kg

Risk of demielinisation and brain injury!!

Hematological emergencies

anemia

trombocytopenia

granulocytopenia

with their consequences

RBC, platelets, granulocytes transfusion as substitution therapy

Timeline of non-infectious complications in organ and hematopoietic stem cell transplantation transplantation.

Lama Elbahlawan et al. Respir Care 2017;62:765-775

(c) 2012 by Daedalus Enterprises, Inc.

Conclusions

Pediatric oncology patients experience a broad variety of critical illnesses related to both disease and therapy

Monitoring, prevention and tretament (using ICU care)can benefit children with malignancies

Thanks for your attention