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Nf and tls

Nf and tls

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Nf and tls

  1. 1. HEMATOLOGIC-ONCOLOGIC EMERGENCIES Neutropenic Fever andTumor Lysis Syndrome
  2. 2.  Tumor Lysis Syndrome  Neutropenic Fever  Leukostasis (pulm and neurotoxicity)  Hypercalcemia  Spinal Cord Compression  SuperiorVena Cava Syndrome
  3. 3. TLS: bags breaking open
  4. 4. TLS: bags breaking open  Hyperkalemia  High uric acid  Hyperphosphatemia  Hypocalcemia  (LDH)
  5. 5. LaboratoryTLS  Hyperkalemia :  25% or ≥ 6.0 mmol/L  Hyperuricemia:  25% or ≥ 8mg/dL  Hyperphosphatemia :  25% or ≥ 4.5 mg/dL  Hypocalcemia:  25% or < 7.0 mg/dL
  6. 6. ClinicalTLS: end-organ damage  Renal Failure  Arrythmias  Seizures  Death: 5-20% of cancer patients
  7. 7. To optimize opportunity and therapy for patients  identify high-risk pts  recognizeTLS early Ideally,Goalis PREVENTION
  8. 8. TLS: Risk factors  Rapidly growing or bulky tumors (LDH)  Hematologic malignancies (AML w/WBC >50K, Burkitt’s, aggressive BCL) - Ki-67: protein cell marker for proliferation  Solid tumors that are advanced or metastatic (lung, breast, GYN, GI, sarcoma, brain) - mortality is 35% - rare  Aggressive poly-chemotherapeutic regimems - cisplatin, cytosine arabinoside, etoposide, methotrexate
  9. 9. TLS: Risk factors  Renal dysfunction/disease (DM2)  Decreased po intake  Nephrotoxic agents (NSAIDs)  First 48-72h  First exposure to a regimen
  10. 10. TLS-Hyperkalemia  ECG: peakedT’s, QT interval abnlities  IVF  **Kayexalate, Lasix If >6.0, then:  Insulin (and D50)  Albuterol  Avoid Ca++gluconate  NaHCO3
  11. 11. Hyperuricemia  Renal Failure: direct tubular damage by uric acid crystallization in kidneys
  12. 12. Hyperuricemia: low risk IVF and prophylaxis  Hydration: IVF - goal urine o/p: 100ml/hr - ideally 48h before chemo  Prophylaxis: Allopurinol - blocks xanthine-oxidase  Alkalinization -encourages conversion to urate salt but also Ca++phos product and ppt of urinary xanthine crystals
  13. 13. Hyperuricemia: High risk  IVF and treatment (also ppx)  Treatment: Rasburicase - recombinant urate-oxidase  allantoin - 5-10 x more soluble  History: in pediatric population - recommended dose: 0.15 or 0.2 mg/kg daily for 3-5 days - we use: 3 mg flat dose ($850/1.5mg)  Precautions: - check g6PD: deficiency is a contraindication - antibody formation: it is a foreign protein. Cloned from Aspergillus - recombinant form: low incidence (pruritis, edema, wheezing), less in nonrecombinant product.
  14. 14. Hyperphosphatemia/hypocalcem ia  Calcium x Phosphate product  calciphylaxis  Goal < 60  Prevention is all  Sevelemer, not Ca++acetate  No Ca++ repletion unless symptomatic (tetany, ms change, arrythmias) - generally if <6.0
  15. 15. Is there a role for HD in TLS? Yes, and they are the same ones you already know  Acidosis, severe metabolic  Electrolyte Abnormalities, persistent  Oliguria/Anuria  Uremia, pericarditis and encephalopathy
  16. 16. Neutropenia and Fever  ANC <500 cells/mm3 or 1000 and trending down  Fever >101 °F (38.3°C) or >100.4 (38.0°C) x 1 hour - oral measurement
  17. 17. Neutrophils = inflammation  FEVER may be only symptom  Even afebrile patients with si/sx of infection should be considered high-risk  Empiric therapy saves lives (culprits)?
  18. 18. NF: Epidemiology and Etiology  Neutropenic Sepsis Mortality: 18-40% (largely due to Pseudomonas)  Bacteremia ~25% -GPC >GNR but latter higher mortality  Negative ID w/u in >50%  Etiology: gut translocation, because of integumentary compromise
  19. 19. NeutropenicFever 1. **WHO: High-Risk groups 2. WHAT: Empiric Antibiotics 3. Antibiotic Modification 4. Antibiotic Duration 5. **WHEN: Antibiotic prophylaxis 6. **WHEN: Empiric Antifungals 7. WHEN: Antiviral prophylaxis 8. WHAT: CSF? 9. **WHAT: Catheter-related infections
  20. 20. NF: Identifyhigh-risk 1. Inpt vs. Outpt 2. Intravenous vs. oral 3. Duration of therapy 4. Hospital access and home support
  21. 21. WHO: High Risk Inpatient 1. Cancer type:AML,ALL, HSCT, hematologic 2. Chemo: induction, consolidation 3. Duration: Neutropenic ≥ 7 days 4. Severity:ANC ≤ 100 cells/mm3 5. Clinical common sense: Hypotension, pna, ms change, new abdominal pain, uncontrolled cancer, s/p mult chemo regimens, advanced age, poor PS 6. Liver or Kidney dysfunction
  22. 22. MASCC score: High risk < 21
  23. 23. NF: WHAT  intravenous  Anti-Pseudomonal - what abx?  Vancomycin -When? Modifications: h/o ESBL (carbapenem), KPC (tigecycline, polymyxin-colistin),VRE (linezolid, dapto)
  24. 24. Low-risk = NOT high-risk  Ciprofloxacin and amoxicillin-clavulanate  4th-generation floroquinolone
  25. 25. Afterstartingempiricantibiotics… 1. When do you stop? 2. When do you change? 3. How long do you treat?
  26. 26. If fevers resolve - Continue abx until ANC ≥ 500 cells/mm3 - Modify regimen according to culture data - D/c empiric vanco if no positive culture after 48h
  27. 27. If persistent fever If stable, continue current regimen Continue to assess for new infection If persistent fever >48-72h or unstable: re-image (CT, MRI, PET) Reculture and consider viral and fungal pathogens Broaden anti-bacterial coverage (MRSA, ESBL), anaerobes Add anti-fungal if >4-7 days
  28. 28. If persistent fever  Mucositis: consider antiviral (HSV) and antifungal (Candida) treatment w/ acylovir and fluconazole, respectively  Typhlitis: GNR (inc Pseudomonas) and anerobic coverage >> antifungal - Surgery consult  Non-infectious…
  29. 29. PersistentFever:non-infectiousddx  Drug-fever  Thrombophlebitis  Tumor/Cancer  Hematoma  PE/thrombus  G-CSF
  30. 30. WHEN: Antifungals  Empiric: consider when 1. fever persistent >4 days 2. CT sinus and chest 3. BDG and AG, PCP DFA and PCR 4. High risk - h/o intensive chemo - s/p HSCT - neutropenic >10 days
  31. 31. WHAT: Antifungals – no particular regimen  If not on ppx: azole, most likely Candida - Candida glabarata and kruseii - amphoterecin B, vori- or itraconazole  If on ppx: usually h/o Aspergillus or at risk (AML pts) - echinocandin, i.e. micafungin - something different from ppx antifungal ~25% given antifungals by these criteria and 4% have invasive fungal infection. [NEJM 2007; 356; 348-59]
  32. 32. WHEN: CSF 1. Prophylaxis when incidence of neutropenia >20% 2. Not generally recommended for treatment of established fever and neutropenia - days of neutropenia, fever, LOS decreased - no mortality benefit * expensive ($350 vs >$5K)
  33. 33. CLABSI 1. If GPC or Pseudomonas, remove catheter. Replace after 48h of negative surveillance cultures 2. if persistently + cultures > 72h 3. Complications: pocket infection, septic thromboses 4. Duration: at least 14d from first negative blood culture 5. Linezolid – can suppress bm, Daptomycin – can raise CPK
  34. 34. Summary 1. Assess Risk - fever may be only symptom - early empiric antibiotics can save lives 1. Persistent fever requires careful and continued reassessment 2. Consider antifungals if fevers >4 days (or new sx, esp. respiratory) 3. CLABSI – Do not pass GO

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