LIFE-THREATENING CONDITIONS
| ONCOLOGIC EMERGENCIES IN PEDIATRIC PRACTICE —Alan S. Wayne, MD, Clinical Director, Pediatric Oncology
Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD
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| Oncologic emergencies: acute complication of cancer; disease or treatment complication that places patient at risk for
life-threatening complications
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| Adopt systematic approach to assessment: recognize that oncologic emergency no different from any other emergency;
strive for balance between diagnosis and intervention; key lies in early recognition and emergent intervention
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| Cardiovascular respiratory emergency: classic chest x-ray of young child with large anterior mediastinal mass;
majority due to leukemia or lymphoma (most common childhood cancer); 10% to 15% of childhood leukemia patients
present with mediastinal mass; majority of T-cell phenotype
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 | Superior vena cava syndrome (SVCS): patient diagnosed with no air movement on right and obstructed superior vena
cava; trachea deviated to left, with large pleural effusion; facial plethora when leaning over; classic presentation
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| Management: must avoid stimulation of cardiovascular and respiratory collapse; try to diagnose while keeping everyone calm
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| Tracheal compression: of greatest concern; may not manage to get child on table for computed tomography (CT); obstruction
can stretch full length of trachea and prevent intubation; cardiothoracic surgery one possible early intervention,
because children may need to go on bypass (however, try to avoid); plain airway film may suffice
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| Making diagnosis: clearly need rapid diagnosis, while at same time stabilizing patient; made noninvasively by draining
pleural fluids under local anesthesia; fluid stain showed acute lymphoblastic leukemia (ALL); diagnosis made in 5
min; patient improved with drainage alone
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| Management: commonly start by looking at smear; avoid intubation; consult radiation oncologist immediately, and hematology
oncology and cardiothoracic surgeon as needed; emergent intervention bedside focused; carry out usual airway,
breathing, and circulation (“ABC”); begin dexamethasone; in most cases, mass “melts” quickly; occasionally
have to resort to irradiation, but try to avoid; need to go through detailed consent forms; challenge of explaining complex
disease (ALL) to child; clinician-patient relationship may involve many years of care
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| Ewing’s sarcoma: effusion moving into tamponade unlikely complication; fluid-filled pericardial sac; signs sometimes
subtle (eg, narrow pulse pressure, rub, distant heart sounds, Kussmaul’s sign, atelectasis, pneumonia); possible success
with chemotherapy before other measures
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| Tumor lysis syndrome: major issue; cancer cells show rapid proliferation and turnover, and once chemotherapy starts,
billions of cells may be lysed; syndrome results from release of intracellular potassium, phosphate, and uric acid that
leads to hyperkalemia with severe risks, hyperphosphatemia that can lead to hypocalcemia and crystallization in kidneys,
and, finally, hyperuricemia with renal failure
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| Risk factors: high tumor burden (evidence found with routine screening, such as large tumor mass or high WBC count in leukemia
patients); rapid cell turnover evidenced in routine full chemistry panel (elevated uric acid, lactate dehydrogenase
[LDH], and creatinine and other electrolyte abnormalities)
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| Management: basic steps; start hydration; maintain good renal blood flow; dilute uric acid; aim for specific gravity <1.010;
alkalinization meant to prevent urate nephropathy but potentially problematic due to risk for phosphate crystallization
in patients with hyperphosphatemia; aim for pH of 7 to 7.5; pH >7.5 increases risk for hypoxanthine crystallization in
kidneys, making for tight range for alkalinization; give intravenous (IV) sodium bicarbonate with hydration to offset;
allopurinol also given immediately
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| Rasburicase (Elitek): urate oxidase; newer antimetabolite; more effective but more expensive than allopurinol
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| Allopurinol: prevents formation of uric acid; monitor electrolytes and fluid balance; keep hypocalcemia in mind; cardiac
and nephrologic monitoring; sometimes modify therapy to make for slow gradual tumor lysis
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| Gastrointestinal (GI) emergencies: ileocecal intussusception can indicate Burkitt’s and other childhood lymphomas;
can result in early surgical cure; neutropenic colitis another complication; dramatic, truly life-threatening (sepsis);
usually after chemotherapy; can show up without fever and with subtle abdominal pain; can escape oncology team;
teaching point is abdominal pain in immunocompromised setting; hospitalize and place on broad-spectrum antibiotics
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| Hematologic: any cancer that infiltrates bone marrow can present with cytopenias (leukemia); take routine complete
blood count (CBC)
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| Absolute neutrophil count (ANC): critical for parent with child starting chemotherapy to understand and know how to
calculate; severity of risk for infection directly related to severity of neutropenia, particularly when ANC <500/mm3 ;
neutropenia or immunosuppression causes blunted inflammatory response (may have no fever response); examine patient
from head to toe; stand patient up on bed and walk around him or her; examine all orifices, wound/drain sites,
signs, and symptoms (eg, slight pain on defecation may indicate perirectal abscess; Aspergillus inoculated around
Band-Aid resulted in loss of patient’s hand [patients leave dressings on until told to remove them])
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| Infection prophylaxis: oncology patients generally at risk for standard infections; prophylaxis includes family education,
good hand washing; routine measures can save lives; influenza vaccine for household members; important to irradiate
and screen blood products to prevent graft-vs-host disease
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| Hyperleukocytosis (elevated white blood cell [WBC] count): >50,000/mm3 ; newly diagnosed; risk for hyperviscosity depends
on subtype of leukemia; looking for signs of leukostasis; 3 target organs (primarily central nervous system
[CNS], respiratory, and renal); infarction most dreaded complication that can become hemorrhagic rapidly due to
thrombocytopenia and/or coagulopathy
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| Management: run O2 saturation test; check for other organ involvement; minimize red blood cell (RBC) transfusion to
avoid relative hyperviscosity, unless patient in extremis; more important to normalize platelet count
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| Major take-home point: give irradiated leukodepleted platelets to patient who arrives with high WBC count before giving
RBCs; initiate therapy; may need to manually lower WBC count (leukapheresis)
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| Spinal cord compression: incidence varies with tumor type (can approach 20%); usually multiply relapsed refractory
end-stage sarcoma; terminal care with paraplegic or quadriplegic miserable beyond description; prevent cord compression
from becoming irreversible nerve damage; epidural mass most common culprit in pediatrics
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| Management: back pain in child must be taken seriously in all instances; palpate back if point tenderness present; imaging
essential; outcome dependent on time of intervention; longer duration makes irreversibility of defects more likely
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| Localize lesion: ask about bowel and bladder function; rapidly move to magnetic resonance imaging (MRI); almost always
start dexamethasone with or without irradiation and occasionally move to laminectomy, depending on underlying
disease
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| From neurologic to psychosocial: speaker cites recent patient with underlying Wiskott-Aldrich syndrome (WAS); rapidly
growing facial mass (high-grade B-cell lymphoma); concerned about ocular function, infection, and CNS leak, but discussing
for psychosocial reasons; child became recluse while cancer growing (stopped going to school and looking in
mirror); clinically, need to act fast in psychosocial arena of depressed child and nervous mother; 6 days after treatment, saw
first smile child mustered in months; demonstrates all of what we do within psychosocial arena; requires systematic and
team approach; early recognition, emergent intervention, and rapid mobilization of full team paramount and essential to successful
outcome
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| APPARENT LIFE-THREATENING EVENTS —Timothy W. Kelly, MD, Clinical Professor of Pediatrics and Director, Core
Clerkship and Intern Selection, Department of Pediatrics, University of California, San Francisco, School of Medicine
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| Apparent life-threatening event (ALTE): difficult important topic; aim should be case-specific differential diagnosis
and evaluation strategy that makes sense for patient
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| Consensus: National Institutes of Health (NIH) consensus development conference put out definition of ALTE; abandoned
terms “nearness SIDS” (sudden infant death syndrome) and “aborted SIDS”
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| Definition (1987): ALTE has combination of elements; frightening to observer, has component of apnea (either central
or obstructive), often color change (cyanotic more than pallor vs red), often change in muscle tone (low to limp), and perhaps
choking or gagging
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| Debate: some thought definition too broad; others feel definition too narrow and fails to account for events relating to mental
status or change of consciousness; frightened or inexperienced caregiver lacking ability to objectively measure or follow case
often provides account of ALTE event; no International Classification of Diseases (ICD)-9 code for ALTE; not diagnosis but
presenting problem or symptom complex that may point to another diagnosis; difficult to track and study
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| Capturing events: differences may occur in way specialty conducts work-up, eg, ALTE admitted to pulmonary service
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| Epidemiology: almost 50% of healthy children monitored in one study had episode of apnea lasting >20 sec; from estimates,
perhaps 1% to 2% of children in general population have ALTE, and fraction might be admitted to hospital
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| Risk factors: maternal smoking and perhaps single-parent household; median age younger than children with SIDS (8
wk); equal boy-girl ratio; SIDS not ALTE and no known causal relationship; only 5% to 10% of SIDS victims had previous
ALTE; clinician taking information after SIDS should consider significant possibility of “recall bias”
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| Mortality: subsequent risk for death among all ALTE patients estimated at most 1% or 2%; dramatically increasing in
rare subgroup of recurrent severe ALTE infants while asleep or who require cardiopulmonary resuscitation (CPR);
clearly highest-risk group; receives most extensive work-up
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| Causes: broad list; based on first presentation and rough estimates from various studies; GI complaints may account for up
to one third of children, eg, gastroesophageal reflux disease (GERD); extraordinarily high prevalence of GERD in this
group (take care not to assign causal relationship); acute gastroenteritis; neurologic conditions, eg, seizures, central apnea,
head injuries, infections; respiratory conditions, particularly respiratory syncytial virus (RSV), pertussis, foreign bodies;
airway conditions, eg, obstructive sleep apnea, stenosis; cardiovascular causes rare (arrhythmia); metabolic, eg, electrolyte
and glucose aberrations, inborn errors of metabolism; seasonal variability; shaken-baby syndrome; child abuse; simple
choking episode; breath-holding; temperature irregularities (eg, infant 42 wk of age left unbundled and gets cold); exaggerated
laryngochemoreceptor reflex apnea associated with reflux or not; also idiopathic or unexplained one of most prevalent
diagnoses
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| Evaluation of ALTE: depends on extraordinarily accurate history; caregiver witness issues may play significant role;
were they present? were events overlooked, distorted, or forgotten? lighting level; how near was witness to baby? what
was covering baby (blankets, sheet, clothes)?
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| Physical examination: examiner must be thorough, focused, and knowledgeable of causes of ALTE; observant of caretaker
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| Tests: no standardized investigative protocol; huge number and challenging array of tests available to clinician; consider
carefully cost, convenience, and risks but most importantly, sensitivity and specificity of each test; perform thoughtful
work-up directed towards possible cause, based on history and physical examination; screening tests may be indicated
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| Management: in cases of ALTE where no apparent cause evident and child appears well, strongly consider hospitalization
for brief monitoring, evaluation, and counseling; treat any identifying cause (eg, for seizure disease, use anticonvulsants)
and infections if found; pediatrician can reinforce back-to-sleep campaign (place healthy babies on their backs to
sleep), which correlated with, if not caused, significant decrease in SIDS; modify other potential risk factors, eg, maternal
smoking, unsafe sleep practices; counsel family; speaker recommends parents take infant CPR course; skills greatly
boost parents’ confidence and preparedness
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| Home monitoring: generally unwarranted; no proven benefit; obstructive airways apnea alarm does not sound until
heart rate below limit (usually 80/min for infants); be aware of adverse effects of home monitoring, including false
alarms leading to anxiety, depression, and hostility; much anxiety around monitoring; 99% of alarms false
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| SIDS case: distinct role for pediatrician; 2 important but different roles; for speaker, pediatrician can play key role; can
delegate this work; work falls into 1) investigation into death and 2) relationship to family as counselor and informant
around tragedy; sense of loss and tremendous emotional upheaval probably affecting pediatrician as well as family;
unique burden of failure to catch something and fear of blame for SIDS death; thorough postmortem investigation as well
as autopsy tailored to SIDS and its uniqueness; look for metabolic errors; think about child abuse; RSV test
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| Protocols for SIDS: clinician can refer to protocols; greatest contribution of clinician simply to not abandon patient
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| Working with family: 10% of pediatricians report not staying in touch with family; stay involved and be available; monitor
grieving process; professional counselor can direct therapy, but pediatrician offering attentive, empathetic listening makes
big difference; stay aware of grieving process; validate grieving response; affected family may talk to physician in way they
cannot talk to family and friends; sit down with family and review autopsy report; help translate, interpret; screen for pathologic
grief
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| Summary: ALTE not infrequent; not specific; generally benign; no true relationship between ALTE and subsequent SIDS;
broad differential diagnosis mandates careful directed history, physical examination, and work-up; definitive cause often not
found, but can be addressed in part by having parents become certified in CPR; home monitoring generally unwarranted and
may inadvertently contribute to morbidity in household
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Educational Objectives
| The goal of this program is to educate the listener about oncologic emergencies in pediatric practice and apparent life-
threatening events (ALTEs). After hearing and assimilating this program, the clinician will be better able to:
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| 1. Describe common oncologic emergencies in overall pediatric oncologic care.
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| 2. Recognize the importance of psychosocial context in oncologic emergencies in pediatric practice.
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| 3. Utilize the contemporary definition of ALTE.
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| 4. Explore the relationship between sudden infant death syndrome (SIDS), ALTE, and other terms.
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| 5. Become adept at creating a case-specific differential diagnosis and evaluation strategy for ALTE.
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Discussed on This Program
Allopurinol [Aloprim, Zyloprim]
Dexamethasone [Aeroseb-Dex, AK-Dex, Decadron, Decadron Phosphate, Decaspray, Dexamethasone Intensol,
Maxidex]
Rasburicase [Elitek]
Suggested Reading
Ali R et al: Superior vena cava syndrome: Initial presentation of acute myeloid leukemia (AML-M0) with near-tetraploidy
+/TdT+/CD7+/CD34+/HLA-DR+. Leuk Lymphoma 47:937, 2006 Bapna A et al: All-trans-retinoic acid (ATRA):
pediatric acute promyelocytic leukemia. Pediatr Hematol Oncol 15:243, 1998; Bernstein M et al: Ewing's sarcoma
family of tumors: current management. Oncologist 11:503, 2006; Cote A: Home and hospital monitoring for ALTE. Paediatr
Respir Rev7 Suppl 1:S199, 2006; Epub 2006 Jun 5. Creutzig U et al: Early deaths and treatment-related mortality
in children undergoing therapy for acute myeloid leukemia: analysis of the multicenter clinical trials AML-BFM 93 and
AML-BFM 98. J Clin Oncol 22:4384, 2004; da Costa CM et al: Cardiac tamponade complicating hyperleukocytosis
in a child with leukemia. Med Pediatr Oncol 33:120, 1999; Hartman GE et al: Management of septic complications
associated with Silastic catheters in childhood malignancy. Pediatr Infect Dis J 6:1042, 1987; Haut C: Oncological
emergencies in the pediatric intensive care unit. AACN Clin Issues 16:232, 2005; Hawes R: Therapeutic relationship
with children and family. Paediatr Nurs 17:15, 2005; Jaing TH et al: Acute myeloid leukemia complicated with staghorn
calculus. Jpn J Clin Oncol 32:365, 2002; Kalwinsky DK et al: Prognostic importance of cytogenetic subgroups
in de novo pediatric acute nonlymphocytic leukemia. J Clin Oncol 8:75, 1990; Katsimpardi K et al: Infections in a pediatric
patient cohort with acute lymphoblastic leukemia during the entire course of treatment. Support Care Cancer
14:277, 2006; Epub 2005 Nov 4. Masjosthusmann K et al: Concomitant Ewing sarcoma and acute lymphoblastic leukemia
in a 5-year-old girl. Pediatr Blood Cancer 45:846, 2005; McCowage GB et al: Granulocyte-macrophage colony-stimulating
factor in association with high-dose chemotherapy (VETOPEC) for childhood solid tumors: a report from
the Australia and New Zealand Children's Cancer Study Group. Med Pediatr Oncol 29:108, 1997; Meech SJ et al: Unusual
childhood extramedullary hematologic malignancy with natural killer cell properties that contains tropomyosin 4--
anaplastic lymphoma kinase gene fusion. Blood 98:1209, 2001; Meyer S et al: Pulmonary dysfunction in pediatric oncology
patients. Pediatr Hematol Oncol 21:175, 2004; Roguin A et al: Fever and neutropenia in children with malignant
disease. Pediatr Hematol Oncol 13:503, 1996; Schrappe M et al: Long-term results of four consecutive trials in
childhood ALL performed by the ALL-BFM study group from 1981 to 1995. Berlin-Frankfurt-Munster. Leukemia
14:2205, 2000; Tabone MD et al: Quality of life of patients treated during childhood for a bone tumor: assessment by
the Child Health Questionnaire. Pediatr Blood Cancer 45:207, 2005; Waseem M et al: Apparent life-threatening event
or child abuse?. Pediatr Emerg Care 22:245, 2006; Yellin A et al: Superior vena cava syndrome associated with lymphoma.
Am J Dis Child 146:1060, 1992
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial relationship
with the manufacturer or provider of any commercial product or service discussed. For this issue, the faculty reported
nothing to disclose.
Dr. Kelly spoke at the 39th Annual Advances & Controversies in Clinical Pediatrics, held June 1-3, 2006, in San
Francisco, CA, and presented by the University of California, San Francisco, School of Medicine, Department of Pediatrics.
Dr Wayne spoke at the Masters of Pediatrics Leadership Conferences on Contemporary and Future Pediatrics
held January 25-30, 2006, in Bal Harbour, FL, and sponsored by the University of Miami Miller School of
Medicine, Department of Pediatrics and Department of Dermatology and Cutaneous Surgery. The Audio-Digest
Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.
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