Ratnoff and Weisman

1
Ratnoff and Weisman

• Alyson Michener, PGY2
• Internal Medicine
• University Hospitals Case Medical Center

2
Logistics

• Ratnoff

• Hem/onc attending
• 1 resident, 2 interns
• Intern cap is 8
• Short, medium, long, happy
• Team room is Seidman 3

• Weisman

• Hem/onc attending or hospitalist
• 1 resident, 2 interns
• Intern cap is 8
• Short, medium, long, happy
• Team room is Seidman 4

3
Common admissions

• Sickle cell
• Pain control, nausea, vomiting
• Failure to thrive
• Cord compression
• Tumor lysis
• Malignancy workup
• Hypercalcemia
• SVC syndrome
• Constipation
• Neutropenic fever
• General medical problems

4
Hints and tricks

• E-mail your patients primary oncologist
• Review oncology notes in portal
• Know treatment history
• Ordering a peripheral smear
• Sickle cell care path, OARRS

5
Ratnoff/Weisman Top 5

1. Neutropenic fever
2. Sickle cell
3. Cord compression
4. Tumor lysis
5. Pain management

6

• A 37-year-old woman is evaluated in the emergency
  department for fever and rigors of 4 hours
  duration. Medical history is significant for
  acute lymphoblastic leukemia for which she
  completed multiagent chemotherapy 10 days ago.
  Her medical history is otherwise noncontributory,
  and she takes no other medications.
• On physical examination, temperature is 38.8,
  blood pressure is 110/60 mm Hg, pulse rate is
  100/min, and respiration rate is 16/min. On
  pulmonary examination, the lungs are clear. The
  remainder of the physical examination is
  unremarkable. Laboratory studies indicate a
  leukocyte count of 0.3µL with 0 neutrophils. The
  remaining laboratory studies are normal.
• A chest radiograph is normal. Blood and urine
  cultures are obtained.
• Which of the following is the most appropriate
  next step in management?
• Administer granulocyte-macrophate
  colony-stimulating factor
• Await culture results before starting
  antimicrobial therapy
• Begin piperacillin-tazobactam
• Begin vancomycin

7
Neutropenic fever

• Neutropenia ANC lt1500 cells/microL Risk of
  infection rises with ANC lt500 cells/microL
• Infectious etiology identified in 20-30 of
  episodes
• Common organisms S. epidermidis, S. aureus,
  Pseudomonas and other gram negatives

8
Neutropenic fever Management

• 2 sets of blood cultures
• Cultures from other sites if clinical suspicion
• CXR if respiratory sx
• Initial monotherapy with zosyn, cefepime, or
  meropenem
• Vancomycin for some indications
• Treatment is typically continued at least until
  ANC gt 500
• Adding antifungals

AG Freifeld et al. Clinical practic guideline for
the use of antimicrobial agents in neutropenic
patients with cancer 2010 update by the
infectious diseases society of america. Clinical
Infectious Diseases. 2011. 52(4) 56-93.
9
Hematopoietic growth factors in neutropenic fever

• G-CSF and GM-CSF
• Can be used prophylactically when risk of
  neutropenic fever is high
• IDSA not recommended for treatment
• ASCO can be considered in some instances

TJ Smith et al. Recommendations for the use of
wbc growth factors american society of clinical
oncology clinical practice guideline update.
Journal of Clinical Oncology. 2015. 3328
(3199-3212)
10

• A 29-year-old man is evaluated in the emergency
  department for dyspnea and diffuse severe pain in
  the arms, legs, back, and chest of 2 days
  duration. He has sickle cell anemia and
  experiences painful episodes one to two times per
  year. He also has a history of acute chest
  syndrome and has known erythrocyte
  alloantibiodies. In addition to increased fluid
  intake at home, he has been taking oral morphine
  sulfate, 30mg twice daily, with no relief. He
  also takes folic acid.
• On physical examination, temperature is 36.8,
  blood pressure is 153/65 mm Hg, pulse rate is
  108/min, and respiration rate is 20/min. Oxygen
  saturation is 98 with the patient breathing
  ambient air. The patient is hunched over in pain,
  and he is diffusely tender to touch.
  Cardiopulmonary, abdominal, and neurologic
  examinations are normal.
• Laboratory studies show hemoglobin 7.2 g/dL,
  leukocyte count 11,900/µL with a normal
  differential, platelet count of 199,000/µL,
  reticulocyte count 5.4, and lactate
  dehydrogenase of 420 units/L. The patient has
  alloantibodies to antigens C, E, and K on blood
  typing and screening.
• In addition to intravenous hydration and
  incentive spirometry, which of the following is
  the most appropriate initial treatment?
• Erythrocyte exchange transfusion
• Erythrocyte transfusion
• Intravenous meperidine
• Intravenous morphine

11
Sickle cell complications

• Pain crisis (vaso-occlusive crisis)
• Acute chest
• Stroke
• MI
• VTE
• Splenic sequestration
• Priapism
• Retinopathy
• Infections

12
Managing a vaso-occlusive crisis

• Labs CBC, retic, LDH, CMP, CRP, UA, TS
• Check for carepath
• Fluids
• Pain medication
• Incentive spirometry

13

• A 21-year-old woman is admitted to the hospital
  with a sickle cell pain crisis. Over the next 48
  hours, she develops worsening dyspnea, chest
  pain, and fever. She takes daily folic acid
  supplementation and morphine delivered by a
  patient-controlled analgesia device with bolus
  and demand infusions.
• On physical exam, temperature is 38, blood
  pressure is 123/65 mm Hg, pulse rate is 118/min,
  and respiration rate is 22/min and labored. There
  is no jugular venous distension. Cardiopulmonary
  exam discloses decreased bilateral breath sound
  at the lung bases, but no crackles or S3. There
  is no peripheral edema.
• Laboratory studies show hemoglobin 6.2 g/dL,
  leukocyte count 6900/µL with a normal
  differential, MCV 84 fL, platelet count
  179,000/µL and reticulocyte count 4.4. Oxygen
  saturation is 86 with the patient breathing
  oxygen, 3 L/min by nasal cannula. Chest
  radiograph shows multilobar infiltrates not
  present on admission chest radiograph. An
  electrocardiogram demonstrates sinus tachycardia
  with no ST changes.
• Broad spectrum antibiotics are begun, incentive
  spirometry is initiated, and morphine is
  continued.
• Which of the following is the most appropriate
  additional treatment?
• Erythrocyte transfusion
• Fluid bolus
• Furosemide
• Hydroxyurea

14
Acute chest

• Fever, chest pain, hypoxemia, wheezing, cough, or
  respiratory distress with a new pulmonary
  infiltrate on CXR
• May see drop in hemoglobin
• Management
• Analgesia
• Oxygen
• Incentive spirometry
• Antibiotics
• Simple transfusion
• Urgent exchange transfusion

Evidence-based management of sickle cell disease.
Expert panel report, 2014. http//www.nhlbi.nih.go
v/sites/www.nhlbi.nih.gov/files/sickle-cell-diseas
e-report20020816.pdf
15
Pain management

• Pain affects 70-80 of patients with advanced
  malignancy
• Pain is often undertreated
• Can be related to the malignancy or the treatment

A Caraceni et al. Use of opioid analgesics in the
treatment of cancer pain evidence-based
recommendations from the EAPC. The Lancet
Clinical Oncology. 2012. 132 (58-68).
16
Assessment of pain

• History
• Pain syndrome
• Pathophysiology and etiology of pain
• Extent of malignancy and plan for further
  treatment
• Goals of care
• Related symptoms

17
Cancer pain syndromes

• Hemorrhage
• Pathologic fracture
• Obstruction/perforation
• Mucositis
• Neuropathy from chemotherapy
• Post radiation
• Tumor invasion

18
Treatment of cancer pain

• Can include disease-modifying therapies and
  symptomatic treatment
• Opioid analgesics
• Non-opioid analgesics
• Adjuvant analgesics
• Non-pharmacologic treatment

19
Opioid analgesia

• Start with short acting
• Tramadol
• Oxycodone
• Hydromorphone
• Patient controlled analgesia
• Transition to a long acting agent
• Palliative care consult

20
Other issues in pain management

• Adjuvant therapy
• Anticonvulsants (gabapentin)
• Antidepressants (desipramine and nortriptyline)
• Corticosteroids
• Opiate side-effects
• Constipation
• Nausea
• Itching

E Bruera and HN Kim. Cancer Pain. JAMA. 2003.
29018 (2476-2479).
21

• A 78-year-old man is hospitalized for a 1-week
  history of progressive and severe back pain and
  weakness in both legs. He describes a sense of
  heaviness in his legs and has had an increasing
  difficulty climbing stairs and getting out of a
  chair. Medical history is significant for
  asymptomatic multiple myeloma that his been
  followed with periodic examinations and
  laboratory studies his last assessment was 3
  months ago and was stable.
• On physical exam, vital signs are normal. He has
  point tenderness over the T10 and T11 vertebral
  bodies, decreased lower extremity muscle strength
  (3/5), increased reflexes isolated to both lower
  extremities, and bilateral extensor plantar
  responses. The remainder of the physical
  examination is unremarkable.
• Laboratory studies are significant for a serum
  hemoglobin level of 6.5 g/dL and a serum calcium
  level of 13mg/dL.
• MRI of the thoracic and lumbar spine shows a
  vertebral body mass and extension into the
  epidural space at T12 and compression of the
  spinal cord.
• Which of the following is the most appropriate
  initial step in treatment?
• Biopsy of the epidural mass
• Decompressive surgery
• IV glucocorticoids
• Multiagent chemotherapy
• Radiation therapy

22
Malignant spinal cord compression

• Compression of the dural sac and its contents
  (spinal cord and/or cauda equina) by an
  extradural tumor mass
• 3 of hospitalized cancer patients per year
• Most commonly seen in lung cancer, breast cancer,
  prostate, multiple myeloma
• 20 initial presentation of malignancy
• Outcome is dependent on pretreatment neurologic
  status

DA Loblaw, J Perry, A Chambers, and NJ
Laperriere. Systematic review of the diagnosis
and management of malignant extradural spinal
cord compression the cancer care ontario
practice guidelines initiatives neuro-oncology
disease site group. Journal of Clinical Oncology.
2005. vol 23 no 9 (2028-2037).
23
Assessment

• Back pain
• Weakness
• Difficulty walking
• Increased deep tendon reflexes
• Bladder and bowel incontinence

24
Management

• MRI entire spine
• High dose dexamethasone (10 mg IV stat followed
  by 4mg Q6)
• Call spine (ortho or neurosurgery)
• Call radiation oncology
• Pain control
• Urinary catheterization

Metastatic spinal cord compression diagnosis and
management of patients at risk of or with
metastatic spinal cord compression. NICE clinical
guidelines, No. 75. 2008.
25

• A 27-year-old man is evaluated in the emergency
  department for a 1-week history of bruising and
  gingival bleeding with flossing. He has no
  significant medical history and takes no
  medications. On physical exam, temperature is
  37.5, blood pressure is 110/80 mm Hg, pulse rate
  is 80/min, and respiration rate is 14/min.
  Scattered ecchymoses and cutaneous petechiae are
  present. There is no lymphadenopathy or
  splenomegaly.
• Laboratory studies
• Peripheral blood smear shows 70 circulating
  myeloblasts.
• Which of the following is the most appropriate
  treatment?
• Fresh frozen plasma
• High-volume normal saline hydration and
  rasburicase
• Multiagent chemotherapy
• Platelet transfusion

Leukocyte count 150,000/µL
Platelet count 20,000/µL
Creatinine 4 mg/dL
Fibrinogen Normal
Phosphorus 8 mg/dL
Urate 12 mg/dL
26
Tumor lysis syndrome

• Metabolic derangements from abrupt release of
  cellular components after rapid lysis of
  malignant cells
• Most common with hematologic malignancies
• Findings
• Hyperuricemia
• Hyperkalemia
• Hyperphosphatemia
• Hypocalecemia
• Uremia
• Acute renal failure

27
Tumor lysis syndrome diagnosis

• CTLS LTLS renal insufficiency,
  arrhthmias/sudden death, seizures

28
Electrolyte derangements

• Hyperphosphatemia nausea, vomiting, diarrhea,
  lethargy, seizures
• Hypocalcemia cardiac arrhythmia, hypotension,
  tetany, cramps
• Hyperkalemia arrhythmias, fibrillation, cardiac
  arrest
• Uremia

29
Management of TLS

• Fluids, fluids, fluids
• Treat hyperkalemia and electrolyte derangements
• Alkalinization?
• Allopurinol
• Rasburicase (recombinant urate oxidase)
• Dialysis

B Coiffier, A Altman, C Pui, A Younes, and MS
Cairo. Guidelines for the management of pediatric
and adult tumor lysis syndrome an evidence-based
review. Journal of Clinical Oncology. 2008.
26(16) 2767-2778.
30
Rasburicase

• Contraindicated in patients with G6PD deficiency
• 0.1-0.2 mg/kg daily for 1-7 days
• Length of therapy based on uric acid levels
• Check uric acid levels 4 hours after
  administration

B Coiffier, A Altman, C Pui, A Younes, and MS
Cairo. Guidelines for the management of pediatric
and adult tumor lysis syndrome an evidence-based
review. Journal of Clinical Oncology. 2008.
26(16) 2767-2778.
31
References

• A Caraceni et al. Use of opioid analgesics in the
  treatment of cancer pain evidence-based
  recommendations from the EAPC. The Lancet
  Clinical Oncology. 2012. 132 (58-68).
• AG Freifeld et al. Clinical practic guideline for
  the use of antimicrobial agents in neutropenic
  patients with cancer 2010 update by the
  infectious diseases society of america. Clinical
  Infectious Diseases. 2011. 52(4) 56-93.
• B Coiffier, A Altman, C Pui, A Younes, and MS
  Cairo. Guidelines for the management of pediatric
  and adult tumor lysis syndrome an evidence-based
  review. Journal of Clinical Oncology. 2008.
  26(16) 2767-2778.
• DA Loblaw, J Perry, A Chambers, and NJ
  Laperriere. Systematic review of the diagnosis
  and management of malignant extradural spinal
  cord compression the cancer care ontario
  practice guidelines initiatives neuro-oncology
  disease site group. Journal of Clinical Oncology.
  2005. vol 23 no 9 (2028-2037).
• E Bruera and HN Kim. Cancer Pain. JAMA. 2003.
  29018 (2476-2479).
• Evidence-based management of sickle cell disease.
  Expert panel report, 2014. http//www.nhlbi.nih.go
  v/sites/www.nhlbi.nih.gov/files/sickle-cell-diseas
  e-report20020816.pdf
• Metastatic spinal cord compression diagnosis and
  management of patients at risk of or with
  metastatic spinal cord compression. NICE clinical
  guidelines, No. 75. 2008.
• TJ Smith et al. Recommendations for the use of
  wbc growth factors american society of clinical
  oncology clinical practice guideline update.
  Journal of Clinical Oncology. 2015. 3328
  (3199-3212)