PHO Emergencies:On-call on 4 West

Maria C. Velez, MDPediatric Hematology-Oncology

LSUHSC/Children’s Hospital

Using case presentation as a learning tool, review frequent urgent scenarios and their management.

Management of electrolyte abnormalities and Tumor Lysis Syndrome (TLS)

Discuss the management of fever in a neutropenic patient

Identify causes of respiratory distress in sickle cell patients

Review the blood product transfusion requirements

Goals and Objectives

11 year old girl presents to ED with 2 days history of high fever (102-103ºF) and leg pain. The CBC shows a WBC=68,000/mm3; Hb=5.9 g/dL; and platelet count=4,000.

• What would you like to do next? (Hint: the fellow and the upper level are in the PICU “really busy” so you “need to figure it out”)

First Phone Call (7:30 PM)

Current concerns?

Physical exam findings

Further tests to order?

What to do next?

What to do next? Current concerns?

• High WBC• Severe anemia• Thrombocytopenia

Further tests to order?• Comprehensive

Metabolic Panel (CMP) Lytes, Mg+2, Phosph,

LDH, uric acid K+=5.8 LDH=5479 Uric acid=9.2 Phosp=7

• CXR

Describe Your Findings

Life-threatening metabolic disturbances Release of intracellular products/ions into

systemic circulation True oncologic emergency Spontaneous or chemotherapy-induced lysis

of malignant cells

Clinical triad

Tumor Lysis Syndrome (TLS)

Tumor Lysis Syndrome (TLS)

Which Clinical Situations Are a Set-up for TLS?

Large tumor burdenHyperleukocytosis

WBC > 50,000Rapidly growing tumor

Burkitt’s Lymphoma (NHL)Large volume or widely

disseminatedLeukemia (ALL > AML)Lymphoma (NHL > HD)Metastatic tumors

Neuroblastoma

Highly sensitive to cytotoxic agents (chemotherapy)

Elevated pre-treatmentSerum uric acidLactate Dehydrogenase

(LDH) (2x upper normal limit)

Hyperkalemia K+ > or = 6 mEq/L

Hyperphosphatemia PO3 > or = 10 mg/L

**Hyperuricemia**Uric acid > or = 10 mg/dLMost important factor in

TLS-associated ARF

When Do U Worry About TLS?

TLS—When You See It, You Believe It!

Alterations in K+, PO3-,

Ca++ & Uric acid• EKG changes

• QRS widening• Peaked T waves

• Cardiac toxicities (arrhythmias)

• Acute renal failure• Elevated Uric Acid--Single

greatest clinical finding in patients who develop TLS-induced acute renal failure

• Sudden death

What fluids would you order and at what rate?

What other therapeutic measures would you initiate?

TLS

Hydration

Alkalinization

Most critical factor in treatment D5 0.2% NS with 40-80 mEq/L

NaHCO3 without K+ (No potassium) 2-4 times the maintenance fluid

volume Consider cardiovascular status and

hemodynamically stable (Hb value)

Maintain urine pH between 7-7.5; adjust NaHCO3 as needed; AVOID urine pH above 7.5Xanthine and hypoxanthine precipitatesCalcium phosphates crystals

Urine output = 100 mL/m2/hr Specific gravity < or = 1.010

TLS: Management—Prevention3

Diuresis

Uric acid reduction

Furosemide (0.5-1 mg/kg) Mannitol (0.5 g/kg over 15 min) Avoid if hypovolemia present

Allopurinol (300 mg/m2/day or 10 mg/kg per day) PO or IV• Inhibits formation of uric acid by

blocking the enzyme xanthine oxidase Urate oxidase (Rasburicase or

Elitek®) [0.15 mg/kg IV daily for 1-5 days]• Converts uric acid to allantoin—

extremely soluble• Does not require alkalinization

TLS: Managing Metabolic Abnormalities

Hyperkalemia

Hyperphosphatemia & Hypocalcemia

**Monitor electrolytes every 6 hrs**

Ion exchange resin (SPS)◦ Kayexelate

Calcium gluconate Hypertonic glucose +

insulin NaHCO3

Loop diuretics Albuterol nebulizer

Phosphate binders Hypocalcemia—will usually

self-correct

TLS: Managing Metabolic Abnormalities

7 Days Post Chemotherapy!

What is your Diagnosis?

T-cell Acute Lymphocytic Leukemia (ALL)

Oncology Patients• Packed Red Blood Cells (PRBC’s)—irradiated,

leukoreduced (leukodepleted), CMV specific (CMV negative for newly diagnosed until status is known)

• 1 U = 250 mL = hematocrit of 65-80% (citrate)• Volume should be ordered in mL per kg

(standard transfusion volume = 10 mL/kg)—raise Hb by 2-2.5 gm/dL (Hct = 6-8%) over 3-4 hrs.

• Transfuse if Hb < 8 g/dL (if clinically stable) Hb < 10 g/dL (if XRT)

Transfusions: When & To Whom

Other conditions• Investigate first• If clinically stable,

monitor closely• If patient needs

transfusion, contact Hematology before transfusion—we can NOT help you for 2-3 months after transfusion!!

When is the best time to check H/H post transfusion?

If transfusion is required:◦ Rule of thumb

mL/kg = g/dL of Hb Hb of 2 g/dL, start with 2

mL/kg very slowly over at least 2 hours and then wait 2 hours before next.

Use diuretics (lasix) Monitor for high output heart

failure

Transfusions: PRBC’s

Always irradiated, leukodepleted, CMV specific, single donor pheresis product over 1 hr◦ < 10 kg—10 mL/kg◦ 10-15 kg—½ unit◦ > 15 kg—1 unit (may volume-reduced to 50 mL)

Obtain 10 minutes or 1 hour post-platelet count Transfuse if

◦ Platelet count < 15-20,000K◦ For brain tumor patients, keep it > 50,000◦ For procedures, keep it > 50,000◦ For port/CL placement >75,000

Platelet Transfusion for Oncology Patients

3 year old child presents to the ED with fever of 100.9ºF for the past 6 hrs. The child was recently diagnosed with stage IV Neuroblastoma and received her first chemotherapy one week ago. Your most appropriate initial medical decision is:A. Describe your approach to this patient

What are you concerned about?Where will you focus your physical exam?

B. Which laboratory tests would you order?C. The physical exam reveals no focus of infection

What therapeutic treatment (s) would you initiate?How does the patient’s ANC (hint) affect your treatment

options?

Second Phone Call 11:45 PM

3 year old child with fever of 100.9ºF and stage IV Neuroblastoma post first chemotherapy one week ago. D. PE reveals a distended, tense, painful

abdomen. ANC=100What are you concerned about?Would you order any additional studies/tests?Which antibiotics would you initiate?

Mediated by proinflammatory cytokines (produced by macrophages and monocytes):

IL-1* TNF-α* IL-6

Inhibit bacterial replication Activation of T and B cells Hepatic synthesis of acute-phase

reactants: C-reactive protein, fibrinogen

Decrease serum iron and zinc Increase serum copper

*Stimulate neutrophils, lymph, monocytes migration; activate chemotaxis, phagocytosis, & killing of bacteria & fungi; mediate development of septic shock

Fever:Define as oral temperature > 38ºC or 100.4ºF

Decrease ability to manifest an inflammatory response• No ANC = No localizing signs

Erythema Pain Swelling

Serious and life threatening infection in the absence of fever

Neutropenic Child

Initial manifestation of infection Medical emergency-untreated patients may

develop devastating complications of bacterial sepsis.

Absolute Neutrophil Count (ANC)• WBC x 103 X {(%seg+%band)/100}

Absolute Phagocytes Count (APC)• WBC x 103 X {(%seg+%band+%mono)/100}

Neutropenia: Moderate --between 500 & 1000Severe--ANC < 500Profound--ANC < 200

Fever in the Neutropenic Child

Neoplastic process itselfInitial manifestation

Leukemia (ALL, AML)Lymphoma (NHL, HD)Neuroblastoma (metastatic)

Drug-inducedAra-C (cytarabine)BleomycinVincristine

Blood product transfusion reaction

***Fever is infection until proven otherwise***

Noninfectious Causes of Fever

Careful history

Meticulous PE (areas at risk) Oropharynx Perianal area Respiratory tract Central venous line

sites Skin and soft tissue Any sites of recent

invasive procedures

CBC, diff & platelet; CMPBlood cultures from all

lumens and peripheral (bacterial, fungal)

Urine culture (clean catch)-but don’t delay therapy for this

Other cultures as clinically indicated (throat, port exit site)

NP aspirate for viral panelChest x-ray—as baseline

CT of the chest BAL (bronchoalveolar lavage)

Evaluation of Child with F/N

Admit for IV Antibiotics (Empirical) STAT• ANC < 500

Cefepime: 150 mg/kg/day (q 8 hrs) (Max.=2 gm per dose)

• Add Vancomycin (60 mg/kg/day q 6-8 hrs) if sepsis is suspected or gram positive organism on gram stain. Adults (< 50 kg): 500 mg IV q 8-12 hrs. (1800

mg/m2/day) Adults (>50 kg): 750-1000 mg IV q 12 hrs. Monitor levels closely.

• Add aminoglycoside for GN organism Monitor levels closely

Management/Treatment of F/N

Antifungals• Micafungin (1-3 mg/kg/day) {Max.=150 mg/day)• Voriconazole (4-6 mg/kg/dose) • Liposomal Amphotericin (3-5 mg/kg/day)• Fluconazole (6 mg/kg/dose)

Fever with ANC>500• Ceftazidime (150 mg/kg/day) every 8 hrs.

schedule

Management/Treatment

Situations where signs and symptoms should be taken VERY seriously even in the absence of fever◦ Abdominal pain (typhlitis)◦ Catheter tunnel infection

Ileoceccal inflammation in neutropenic patients

Management• Broad spectrum

antimicrobials Meropenem Flagyl Vancomycin Antifungal

• NPO• TPN—for adequate nutrition

• CT scan (w contrast)• KUB (baseline)

Typhlitis = Neutropenic Colitis

Pulmonary Infections

PCP in immunocompromised patient

Fungal Pneumonia

3 year old child presents to the ED with fever of 100.9ºF for the past 6 hrs. The child was recently diagnosed with stage IV Neuroblastoma and received his first chemotherapy one week ago. Your most appropriate initial medical decision is:

A. Give acetaminophen because you are concerned about febrile seizures.

B. Argue with the mother because it took her so long to get to the ED

C. Ask the parent to sit in the waiting area until it is their turn to be seen (100.9ºF is not that high!)

D. Panculture the child and start broad spectrum antibiotics STATE. Repeat a rectal temperature to confirm that the child is indeed

febrile.

Back to our Problem

3 year old child presents to the ED with fever of 100.9ºF for the past 6 hrs. The child was recently diagnosed with stage IV Neuroblastoma and received his first chemotherapy one week ago. Your most appropriate initial medical decision is:A. Give acetaminophen because you are concerned about febrile

seizures.B. Argue with the mother because it took her so long to get to

the EDC. Ask the parent to sit in the waiting area until it is their turn to

be seen (100.9ºF is not that high!)

D. Panculture the child and start broad spectrum antibiotics STAT

E. Repeat a rectal temperature to confirm that the child is indeed febrile.

We Have a Solution

A 16 year old male with sickle cell disease (Hb SS) presents with 1 day history of upper back and leg pain, cough, subjective fever, and shortness of breath. The child looks in moderate distress, pale, and diaphoretic. ◦ Describe your approach to this patient

What are you concerned about? Which laboratory tests would you order?

Third Phone Call (2:55 am)

Acute Chest Syndrome (ACS) vs. Pneumonia (PNA)

Proposed etiologies or pathogenesis of this condition

Acute Chest Syndrome (ACS) in Sickle Cell Disease

Leading cause of morbidity & mortality

2nd most common complication (pain is 1st)

Highest incidence in children ages 2-4 years

Prognosis—poor• Death rate 4x higher in

adults vs. children

Most common etiologies• Infection

Mycoplasma Chlamydia Virus Bacterial

S. pneumoniae-58% Haemophilus-18%

• Bone marrow/fat embolus-during acute VOC (pain) crises

• Unknown-16%

ACS/PNA

List all of the therapeutic options for this condition

ACS/PNA

PRBC’s transfusion-Simple transfusion vs. exchange transfusion• Decrease sickling• Improve oxygenation

Oxygen therapy Antibiotics

• Against encapsulated organisms 3rd generation

cephalosporine—Ceftriaxone Vancomycin

• Macrolides

Analgesia• Opioids

PCA +/- basal Scheduled vs. PRN

• Anti-inflammatories NSAIDS

Hydration status• ¾ maintenance

Bronchodilator therapy• 73% with airway

hyperactivity

ACS Management

Sickle Cell Patients• Know their baseline

status!!• Acute Chest Syndrome• Pneumonia• Aplastic Crisis• Splenic Sequestration• CVA-stroke

PRBC’s are leukodepleted, Sickle Cell free• No need for irradiation

Transfusions: PRBC’s

A 7 year old child with sickle cell disease (Hb SS) presents with 1 day history of chest pain, cough, subjective fever, and shortness of breath. The child looks in moderate distress, pale, and diaphoretic. The following are all correct except:A. Start morphine PRN for the painB. Order CBC, retic, CMP, and type/matchC. IV bolus with 20 mL/kg over 10-15 minutesD. Get CXR and pulse oxymetryE. IVF’s at ¾ maintenance

A 7 year old child with sickle cell disease (Hb SS) presents with 1 day history of chest pain, cough, subjective fever, and shortness of breath. The child looks in moderate distress, pale, and diaphoretic. The following are all correct except:A. Start morphine PRN for the painB. Order CBC, retic, CMP, and type/match

C. IV bolus with 20 mL/kg over 10-15 minutes

D. Get CXR and pulse oxymetryE. IVF’s at 3/4 maintenance

Questions?

Montones Beach Isabela, Puerto Rico

Questions?

El Yunque Rain Forest, Luquillo, Puerto Rico

5 year old child presents with this rash.

Describe the Rash!

Low Platelets

Observation IVIg

• 1 g/kg/day up to 50 g/dose WinRho

• Only for Rh + patients Steroids

• 2 mg/kg/day X 14 days Rituximab

Immune Thrombocytopenia Purpura (ITP)