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PHO Emergencies: On-call on 4 West. Maria C. Velez, MD Pediatric Hematology-Oncology LSUHSC/Children’s Hospital. Goals and Objectives. Discuss the management of fever in a neutropenic patient Identify causes of respiratory distress in sickle cell patients

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pho emergencies on call on 4 west

PHO Emergencies:On-call on 4 West

Maria C. Velez, MD

Pediatric Hematology-Oncology

LSUHSC/Children’s Hospital

goals and objectives
Goals and Objectives
  • Discuss the management of fever in a neutropenic patient
  • Identify causes of respiratory distress in sickle cell patients
  • Review the blood product transfusion requirements
  • Using case presentation as a learning tool, review frequent urgent scenarios and their management.
  • Management of electrolyte abnormalities and Tumor Lysis Syndrome (TLS)
first phone call 7 30 pm
First Phone Call (7:30 PM)
  • 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”)
what to do next
What to do next?
  • Current concerns?
  • Physical exam findings
  • Further tests to order?
what to do next5
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
tumor lysis syndrome tls
Tumor Lysis Syndrome (TLS)
  • 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
when do u worry about tls
When Do U Worry About TLS?
  • Elevated pre-treatment
    • Serum uric acid
    • Lactate Dehydrogenase (LDH) (2x upper normal limit)
  • Hyperkalemia
    • K+ > or = 6 mEq/L
  • Hyperphosphatemia
    • PO3 > or = 10 mg/L
  • **Hyperuricemia**
    • Uric acid > or = 10 mg/dL
    • Most important factor in TLS-associated ARF
  • Large tumor burden
    • Hyperleukocytosis
      • WBC > 50,000
    • Rapidly growing tumor
      • Burkitt’s Lymphoma (NHL)
    • Large volume or widely disseminated
      • Leukemia (ALL > AML)
      • Lymphoma (NHL > HD)
      • Metastatic tumors
        • Neuroblastoma
    • Highly sensitive to cytotoxic agents (chemotherapy)
tls when you see it you believe it
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
slide12
TLS
  • What fluids would you order and at what rate?
  • What other therapeutic measures would you initiate?
tls management prevention 3
TLS: Management—Prevention3
  • 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 7.5
    • Xanthine and hypoxanthine precipitates
    • Calcium phosphates crystals
  • Urine output = 100 mL/m2/hr
  • Specific gravity < or = 1.010
  • Hydration
  • Alkalinization
tls managing metabolic abnormalities
TLS: Managing Metabolic Abnormalities
  • 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 xanthineoxidase
  • Urateoxidase (Rasburicase or Elitek®) [0.15 mg/kg IV daily for 1-5 days]
    • Converts uric acid to allantoin—extremely soluble
    • Does not require alkalinization
  • Diuresis
  • Uric acid reduction
tls managing metabolic abnormalities15
TLS: Managing Metabolic Abnormalities
  • Ion exchange resin (SPS)
    • Kayexelate
  • Calcium gluconate
  • Hypertonic glucose + insulin
  • NaHCO3
  • Loop diuretics
  • Albuterol nebulizer
  • Phosphate binders
  • Hypocalcemia—will usually self-correct
  • Hyperkalemia
  • Hyperphosphatemia & Hypocalcemia
  • **Monitor electrolytes every 6 hrs**
7 days post chemotherapy

What is your Diagnosis?

T-cell Acute Lymphocytic Leukemia (ALL)

7 Days Post Chemotherapy!
transfusions when to whom
Transfusions: When & To Whom
  • 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 prbc s
Transfusions: PRBC’s
  • 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
  • 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?
platelet transfusion for oncology patients
Platelet Transfusion for Oncology Patients
  • 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
second phone call 11 45 pm
Second Phone Call 11:45 PM
  • 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?
slide21

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=100
      • What are you concerned about?
      • Would you order any additional studies/tests?
      • Which antibiotics would you initiate?
fever define as oral temperature 38 c or 100 4 f
Fever:Define as oral temperature > 38ºC or 100.4ºF
  • *Stimulate neutrophils, lymph, monocytes migration; activate chemotaxis, phagocytosis, & killing of bacteria & fungi; mediate development of septic shock
  • 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
neutropenic child
Neutropenic Child
  • 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
fever in the neutropenic child
Fever in the 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 & 1000
    • Severe--ANC < 500
    • Profound--ANC < 200
noninfectious causes of fever
Noninfectious Causes of Fever
  • Neoplastic process itself
    • Initial manifestation
      • Leukemia (ALL, AML)
      • Lymphoma (NHL, HD)
      • Neuroblastoma (metastatic)
  • Drug-induced
    • Ara-C (cytarabine)
    • Bleomycin
    • Vincristine
  • Blood product transfusion reaction
  • ***Fever is infection until proven otherwise***
evaluation of child with f n
Evaluation of Child with F/N
  • CBC, diff & platelet; CMP
  • Blood 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 panel
  • Chest x-ray—as baseline
    • CT of the chest
    • BAL (bronchoalveolarlavage)
  • 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
management treatment of f n
Management/Treatment of 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
Management/Treatment
  • 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
slide31

Situations where signs and symptoms should be taken VERY seriously even in the absence of fever

    • Abdominal pain (typhlitis)
    • Catheter tunnel infection
typhlitis neutropenic colitis
Typhlitis = Neutropenic Colitis
  • Ileoceccal inflammation in neutropenic patients
  • Management
    • Broad spectrum antimicrobials
      • Meropenem
      • Flagyl
      • Vancomycin
      • Antifungal
    • NPO
      • TPN—for adequate nutrition
    • CT scan (w contrast)
    • KUB (baseline)
pulmonary infections
Pulmonary Infections

PCP in immunocompromised patient

Fungal Pneumonia

back to our problem
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 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 STAT

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

we have a solution
We Have a Solution
  • 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 STAT

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

third phone call 2 55 am
Third Phone Call (2:55 am)
  • 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?
proposed etiologies or pathogenesis of this condition
Proposed etiologies or pathogenesis of this condition
  • Acute Chest Syndrome (ACS) vs. Pneumonia (PNA)
acs pna
ACS/PNA
  • Most common etiologies
    • Infection
      • Mycoplasma
      • Chlamydia
      • Virus
      • Bacterial
        • S. pneumoniae-58%
        • Haemophilus-18%
    • Bone marrow/fat embolus-during acute VOC (pain) crises
    • Unknown-16%
  • 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
acs pna40
ACS/PNA
  • List all of the therapeutic options for this condition
acs management
ACS Management
  • Analgesia
    • Opioids
      • PCA +/- basal
      • Scheduled vs. PRN
    • Anti-inflammatories
      • NSAIDS
  • Hydration status
    • ¾ maintenance
  • Bronchodilator therapy
    • 73% with airway hyperactivity
    • PRBC’s transfusion-Simple transfusion vs. exchange transfusion
    • Decrease sickling
    • Improve oxygenation
  • Oxygen therapy
  • Antibiotics
    • Against encapsulated organisms
      • 3rd generation cephalosporine—Ceftriaxone
      • Vancomycin
    • Macrolides
transfusions prbc s42
Transfusions: PRBC’s
  • 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
slide43

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 pain

B. Order CBC, retic, CMP, and type/match

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

D. Get CXR and pulse oxymetry

E. IVF’s at ¾ maintenance

slide44

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 pain

B. Order CBC, retic, CMP, and type/match

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

D. Get CXR and pulse oxymetry

E. IVF’s at 3/4 maintenance

questions
Questions?

Montones Beach

Isabela, Puerto Rico

questions46
Questions?

El Yunque Rain Forest,

Luquillo, Puerto Rico

describe the rash
Describe the Rash!
  • 5 year old child presents with this rash.
immune thrombocytopenia purpura itp
Immune Thrombocytopenia Purpura (ITP)
  • 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