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MORBIDITY and MORTALITY CONFERENCE

MORBIDITY and MORTALITY CONFERENCE. Anna M. Dapul, M.D. Kathleen B. Miranda, M.D. August 12, 2010. OBJECTIVES. To present a case of pneumonia in a Chronic Lymphocytic Leukemia patient; To discuss the infectious complications in CLL patients

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MORBIDITY and MORTALITY CONFERENCE

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  1. MORBIDITY and MORTALITY CONFERENCE Anna M. Dapul, M.D. Kathleen B. Miranda, M.D. August 12, 2010

  2. OBJECTIVES • To present a case of pneumonia in a Chronic Lymphocytic Leukemia patient; • To discuss the infectious complications in CLL patients • To discuss the syndrome of Transfusion-related Acute Lung Injury

  3. DATA • E.B. • 71/male • Difficulty of breathing

  4. HISTORY OF PRESENT ILLNESS • 1 week PTA  • 2 days PTA  • 1 day PTA  • Few hours PTA  • Cough self-medicated w/unrecalled antibiotics • Colds, watery nasal discharge • Productive cough • Fever T=39C • OPD HSP consult, given Paracetamol, Levofloxacin 750mg OD • DOB  ER Admitted

  5. REVIEW OF SYSTEMS • General: (-) weakness, (-) weight changes, (-) night sweats, (-) fever, (-) syncope • Skin: (-) pruritus, (-) rashes, (-) easy bruising, (-) telangestasia, (-) spiderangiomatas • HEENT: (-) headache, (-) dizziness, (-) BOV, (-) eye redness, (-) epistaxis, (-) deafness, (-) ear discharge, (-) bleeding gums, (-) oral sores, (-) hoarseness, (-) neck pain, (-) limitation of motion

  6. REVIEW OF SYSTEMS • Respiratory: (-) hemoptysis, (-) PND • Cardiovascular: (-) chest pain, (-) palpitations, (-) orthopnea, (-) paroxysmal nocturnal dyspnea • Gastrointestinal: (-) dysphagia, (+) early satiety, (-) jaundice, (-) nausea, (-) vomiting, (-) hematemesis, (-) constipation, (-) diarrhea

  7. REVIEW OF SYSTEMS • Genitourinary: (-) polyuria, (-) hematuria, (-) nocturia, (-) oliguria, (-) dysuria • Extremities: (-) joint pains, (-) swelling • Neurologic: (-) seizures, (-) tremors, (-) involuntary movements • Hematologic: (-) dizziness, (-) bleeding, (-) easy bruising • Endocrinologic: (-) occasional excessive sweating, (-) polyphagia, (-) polyuria, (-) polydipsia

  8. PAST MEDICAL HISTORY Chronic Lymphocytic Leukemia(B-Cell)-2007 • On intermittent oral chemotherapy with Chlorambucil, Prednisone, Folic Acid, and Multivitamins • Hypertension x 5years • On Amlodipine 10mg tab OD • Metoprolol 100mg OD • Usual BP: 120/90; highest BP140/90 • No known allergies; no previous surgeries

  9. FAMILYHISTORY • Hypertension- mother SOCIAL HISTORY • 20 pack year smoker • Occasional alcoholic beverage drinker

  10. PHYSICAL EXAMINATION • Conscious, coherent • BP= 130/80 HR=107RR=18 T=36.8C O2 SAT = 94% (room air) • Pale palpebral conjunctivae, anicteric sclera, no tonsillopharyngeal congestion, no cervical lymphadenopathy, no oral thrush • Equal chest expansion, no retractions, bibasal crackles, no wheezes

  11. PHYSICAL EXAMINATION • Adynamic precordium, normal rate, regular rhythm, distinct S1 and S2, no appreciated murmurs • Flabby abdomen, soft abdomen, normoactive bowel sounds, no tenderness, no splenomegaly • No gross deformities of the extremities, pulses full and equal, no cyanosis, no edema

  12. SALIENT FEATURES 71/male Dyspnea Fever Productive cough Known case of Chronic Lymphocytic Leukemia ~3years Tachypnea Pale palpebral conjunctivae Bibasal rales

  13. ADMITTING IMPRESSION • Community Acquired Pneumonia in an Immunocompromised Host • Chronic Lymphocytic Leukemia • Hypertensive Atherosclerotic Cardiovascular Disease

  14. An Immunocompromised Host • Immunocompromised host • Alteration in phagocytic, cellular, or humoral immunity • Increased risk for an infectious complication or an opportunistic process (ie lymphoproliferative disorder or cancer) • Alteration or breach of skin or mucosal defense barriers that permits microorganisms to cause either a local or systemic infection (ie indwelling catheters, burns) Pizzo, P. Fever in Immunocompromised Patients.NEJM.1999;341: 893

  15. Pneumonia in an Immunocompromised Patient

  16. Chronic Lymphocytic Leukemia • Disease affecting neoplastic B cells • Mostly asymptomatic • Common symptoms: lymph node enlargement, constitutional symptoms, bone marrow failure • Mainly affects elderly (median age=72 yrs)

  17. Chronic Lymphocytic Leukemia • Clinical diagnosis: absolute lymphocytosis with lower threshold of >5000 mature-appearing lymphocytes/uL

  18. STAGING OF TYPICAL B CELL LYMPHOID LEUKEMIA

  19. STAGING OF TYPICAL B CELL LYMPHOID LEUKEMIA

  20. Inherent Immune Defects in patients with Chronic Lymphocytic Leukemia Hypogammaglobulinemia Inhibition in B-cell proliferation Cell-mediated immune defects Functional abnormalities of T-lymphocytes, nonclonal CD5– B lymphocytes Abnormalities in T-cell subsets, with a decreased CD4/CD8 ratio Excessive T-suppressor and deficient T-helper cell function Downregulated T-cell function Defects in NK-cell, lymphocyte-activated killer cell activity Reduced T-cell colony-forming capacity Defective antibody-dependent cytotoxicity Defective delayed hypersensitivity responses

  21. Defects in complement activity Reduction in complement component levels Defects in complement activation and binding Neutrophil defects Defects in neutrophil function (phagocytic, bactericidal activity, chemotaxis) Reduced absolute neutrophil count Monocyte defects (deficiencies in β-glucuronidase, lysozyme,myeloperoxidase) Potential mucosal immune defects

  22. At the ER Chills, bibasal rales ECG: sinus tachycardia Hypotensive episode Admitted under ID service Oxygen at 4 LPM Referred to: nephrology, cardiology, hematology services dopamine drip-5mcg (200mg/100ml)

  23. CXR (3/30) cardiomegaly with pulmonary congestion

  24. Infectious Disease • Blood gs/cs, sputum gs/cs, urine gs/cs, urinalysis • Piperacillin-Tazobactam 2.25g IV q8 hours • Cardiology • 2D ECHO, specM, Trop I/T, D dimer • Hematology • Prepare 2u pRBC • Start Chlorambucil 2mg tab TID • Nephrology • ABGs, Na, K, crea, Mg, Ca • For central line insertion • Furosemide 40mg 2tabs BID • Limit OFI 1-1.5L/day

  25. At the ER

  26. 1ST Hospital Day • S> no complaints, comfortable at o2 of 2 LPM; post 1 unit PRBC • O> BP90-110/60-70 on dopamine drip, HR=95-110, crackles mid-base L>R, T=38.2C I&O=1275 vs 1400

  27. CXR (4/1) clearing of pulmonary congestion, hazy infiltrates with some cystic lucencies in LLL probably due to pneumonia with underlying bronchiectasis

  28. 1ST Hospital Day • 2D Echo: IVSH, NWMC, EF=63%, mild MR, reversed mitral E/A ratio and prolonged IVRT indicative of decreased LV relaxation • Blood, urine, sputum CS: no growth x 24hrs • UA: normal • Piperacillin Tazobactam – day1

  29. Complications of CLL • Infections • Hematologic abnormalities: • anemia (autoimmune hemolytic anemia) • pure red cell aplasia • thrombocytopenia • Richter Syndrome or Richter transformation • refers to the transformation of CLL into an aggressive large B-cell lymphoma

  30. Infectious Complications of CLL • Leading cause of mortality in 25-50% • Pathogenesis of infection is multifactorial • Major risk factor: inherent immune defects and therapy-related immunosuppression

  31. Treatment • Front-line treatment usually involves purine analogue such as Fludarabine in combination with Cyclophosphamide combined with monoclonal antibodies such as Rituximab • Chlorambucil is considered standard treatment for elderly patients due to easier administration and less immunosuppression • Zenz, T et. al. Treatment of CLL in Older Patient. Medscape CME Oncology.2010

  32. The Impact of Chronic Lymphocytic Leukemia Therapy on the Spectrum of Infection

  33. 2nd Hospital Day • S> awake, conversant, no febrile episodes, D2 piperacillin-tazobactam • O> BP90-110/60-70 HR=90-100, crackles L>R, Total I&O= 4030 vs 3500 on furosemide 80mg bid Blood CS: no growth x 48 hours • Urine & Sputum CS: no growth x 48hrs

  34. CXR (4/2) complete clearing of pulmonary congestion, rest of the chest findings are unchanged

  35. 2nd Hospital Day • Piperacillin-Tazobactam shifted to Levofloxacin 500mg PO x 1 dose then 250mg PO q48 hours • Started Metronidazole 500mg PO q8 hours • Furosemide decreased to 80mg PO q24 hours • Patient referred back to prior hematologist

  36. IV to Oral Switch Therapy • De-escalation of initial empiric broad-spectrum antibiotic to oral agent based on available laboratory data is recommended once the patient is • clinically improving • hemodynamically stable • functioning gastrointestinal tract • Community-Acquired Pneumonia Clinical Practice Guidelines 2010 Update

  37. Pharmacoeconomics of IV to PO Therapy Conversion • One study that specifically focused on levofloxacin found proactive conversion to the oral formulation reduced length of stay by 3.5 days and saved medication/supply costs • Another recent study documented that early conversion from IV to PO therapy in CAP decreased length of stay by almost 2 days, while having no negative effects on mortality or clinical cure • Kuper, K. Intravenous to Oral Therapy Conversion. Competence Assessment Tools for Health-System Pharmacies 4th Ed. 2008:347.

  38. 3rd Hospital Day • S> awake, coherent, fever • O> Tmax=38.3C BP90-120/60-70 on dopamine, HR=90-120, Total I&O 2565 vs 3400 • UA: normal • Repeat blood CS taken • Furosemide held • Paracetamol as needed for fever • Cefepime 1gram q24 hrs

  39. CXR (4/3) taken in poor inspiratory effort, increase in left lower lung infiltrates

  40. 4th Hospital Day • S> denied chest pain, dob • O> BP90-108/60-70 on dopamine, HR=100-115, Tmax=38.5C, 02sat=88% @ 4lpm Total I&O= 2859 vs 2000 • Blood CS: no growth x 24 hours • ABG taken

  41. 4th Hospital day • Shifted to MVM 0.50 • Pulmonary referral • Imp: Pneumonia in the immunocompromised, T/C COPD, R/O Pulmonary Embolism • Started Acetylcysteine, Ipratropium, Enoxaparin 40mg SQ OD, Doxofylline

  42. 5th Hospital Day • S>(0850H) dyspneic • O> BP90-100/60-80 on dopamine, HR=105-150, 02sat=84-88%, crackles L>R • MVM shifted to in-line neb 70%

  43. CXR (4/5) accentuation of pulmonary vasculature consistent with congestion, increase haziness in left base

  44. 5th Hospital Day • (1200H)Hydrocortisone 200mg Furosemide 120mg • In-line neb  BiPAP  intubated • (1305H) sustained V. tach  defibrillation 360J x3, amiodarone drip

  45. 5th Hospital Day • S> (1600H) drowsy-stuporous • O> BP 88/60, HR=145, narrow QRS tachycardia at 145bpm • Meropenem started 500mg IV OD • Blood and tracheal aspirate CS • Femoral line inserted, initial cvp=8 • Hydrocortisone 50mg IV TID, furosemide 40mg IV TID

  46. 6th Hospital day • S> awake, febrile • O> BP 80-120/40-80 on Dopamine, HR=130-140s on Amiodarone drip, Tmax=39.8C 02sat=93-95% at AC mode 100% • (1705H): unresponsive, GCS=3, pupils anisocoric, BP 70/50, HR=140s, CVP=5-6  norepinephrine drip • Referred to neurology service • Imp: T/C ICH, left with herniation

  47. 6th Hospital day • (2200H): S> comatose • O> BP60 palpatory on Dopamine and Norepinephrine, HR=110s, 02sat=85% at AC mode100% • DNR form signed • (2238H): Expired • Blood CS: candida albicans

  48. Final Diagnosis • Cardiopulmonary Arrest secondary to Septic Shock secondary to Severe Pneumonia with Candidemia in an immunocompromised host • Transfusion related acute lung injury • Chronic Lymphocytic Leukemia

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