Case Report: Severe Infusion Reaction to Rituximab
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Case Report: Severe Infusion Reaction to Rituximab






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  • Patient was given another dose of EpiPen and more fluids. Propofol was started in order to put central line. However the blood pressure dropped to 74/52, Vasporessin was added on and dose of Propofol decreased. Famotidine was given to complete allergic reaction treatment, that is usually consists of Bendarly, Solumedrol and PepcidBitting on the tube propofol given
  • Severe hyperkalemia: K >7
  • CaCl preferably via a central line.CaCL contain three times the concentration of elemental Ca compared to Ca gluconate (13.6 vs 4.6 meq in 10 ml of 10 % solution) The effect of intravenous calcium administration begins within minutes but is relatively short-lived (30 to 60 minutes). As a result, calcium should not be administered as monotherapy for hyperkalemia but should rather be combined with therapies that drive extracellular potassium into cells
  •  Lactic acidosis is the most common cause of metabolic acidosis in hospitalized patients. It is associated with an elevated anion gap and a plasma lactate concentration above 4 meq/L. Impaired tissue oxygenation, leading to increased anaerobic metabolism, is usually responsible for the rise in lactate production. Lactic acidosis causes a decrease in serum bicarbonate concentration that is similar in magnitude to the increase in the lactate concentration. Lactate is a metabolizable organic anion that, when oxidized, will generate bicarbonate
  • Patients with lactic acidosis and severe academia receive bicarbonate therapyThe primary aim of therapy is reversal of underlying disease. When using bicarb therapy in patients with lactic acidosis and severe academia the aim is to maintain the arterial pH >7. What is the normal pH 7.35-7.45Alternative of agents Carbicarb, thromethiamine
  • RITUXAN can cause severe, including fatal, infusion reactions. Severe reactions typically occurred during the first infusion, with time to onset of 30-120 minutes. Can occur: hypotension, angiodema, hypoxia, bronchospasm, pulmonary infiltrates, acute respiratory distress syndrome, MI, ventricular fibrillation, anaphylactoid evens, or deathAcute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia from tumor lysis, some fatal, can occur within 12-24 hours after the first infusion of RITUXAN. A high number of cirulating malignant cells ((≥25,000/mm3) or high tumor burden confers a greater risk of TLS
  • ABVD- Adriomycin (doxorybicin), bleomycin, vinblastin , dacarbazine

Case Report: Severe Infusion Reaction to Rituximab Case Report: Severe Infusion Reaction to Rituximab Presentation Transcript

  • SEVERE INFUSION REACTION TO RITUXIMAB CASE REPORT Hanna Yudchyts, Pharm D. PGY-1 Pharmacy Resident NSLIJ Lenox Hill Hospital
  • Objectives  Introduce patient case  Discuss metabolic abnormalities  Hyperkalemia  Lactic acidosis  Learn about Rituximab  Review infusion reaction  Discuss possible Tumor Lysis Syndrome (TLS)
  • History of Present Illness  Chief complaint: Anaphylaxis  HPI: JL is a 73 y/o F who presented to LHH Emergency Department from oncology infusion center on 08/14/13 with anaphylaxis to Rituximab. During first infusion, she experienced nausea and vomiting. The infusion was stopped. Patient noted to have some shortness of breath and tongue swelling. EMS was called at 14:35. EMS arrived on the scene at 14:38.
  • Past Medical History  Non-Hodgkin’s Lymphoma • Mantle cell lymphoma, blastoid variant • No previous treatment received  Diabetes Mellitus type 2  Hypertension  Hypercholesterolemia  Home Medications  Losartan  Metformin  Glipizide  Fenofibrate  Ezetimibe/Simvastatin
  • EMS Finding and Actions  Vital signs  Medications administered  Epinephrine 0.3 mg IM  Diphenhydramine 50 mg IV  Methylprednisolone 125 mg IV  Normal Saline 1 L IV  No improvement  mental status decreased to unresponsive. Patient was intubated and brought to LHH emergency department at 15:30. BP Pulse RR SpO2 BS 81/59 130 36 78 211
  • Upon Arrival at Emergency Department Stat medications given at 16:22  Sodium Chloride 0.9% IV 1 L bolus  Epinephrine 0.3 mg IM  Famotidine 20 mg IV  Propofol 5 mcg/kg/min, titrate to acceptable sedation  Vasopressin 40 units IV
  • Initial Findings 89.8 617.5 24.8 214 Lactic Acid pH CO2 HCO3 15.2 6.79 58 9 130 99 38 8.2 8 4.05 •Urinalysis and blood cultures are negative •ECG: wide complex tachycardia Lab values received between 16:42-17:11
  • Metabolic Abnormalities
  • Hyperkalemia  Severe hyperkalemia can lead to:  Muscle weakness or paralysis  Cardiac conduction abnormalities  Cardiac arrhythmias  Treatment approaches:  Antagonizing the membrane effects of K+ with Ca2+  Driving extracellular K+ into the cells  Removing excess K+ from the body
  • Stabilize Cardiac Membranes with Calcium  Significant ECG findings or severe arrhythmias  Calcium Chloride  500-1000 mg  Calcium Gluconate  1000 mg • IV infusion over 2-3 min  Effect of Ca2+ is transient  treatments to shift K+ into cells and to remove K+ are required
  • Shift Potassium into Cells  Insulin+ Glucose  Regular Insulin 10 units IV bolus + 50 ml of D50W  Beta 2 agonist  Albuterol 10-20 mg in 4 ml saline via nebulizer  Sodium Bicarbonate  Minimal effect on shifting K+ intracellularly  150 mEq in 1 L of D5W in water at 250 ml/h  The effect of shifting K+ into the cells is transient, treatments to remove K+ are also required
  • Strategies for Eliminating Potassium  Sodium Polystyrene Sulfonate (Kayexalate®)  Cation exchange resin  15-30 g PO  Diuretic  Limited short-term effect  Furosemide 20-40 mg IV  Hemodialysis  If above measures failed  Hyperkalemia is severe  Patient with renal failure  Marked tissue breakdown large amount of K+ released form injured cells
  • Lactic Acidosis  Common cause of metabolic acidosis  Elevated plasma lactate concentration (> 4meq/L)  Elevated anion gap Impaired tissue oxygenation Increased anaerobic metabolism Rise in lactate production Decrease in serum bicarbonate concentration Decrease in pH Metabolic acidosis
  • Acidosis Treatment  Who should be treated  pH < 7.10  Goal of therapy  Reversal of underlying cause  Goal for arterial pH > 7.10  Approach  1-2 mEq/kg Sodium Bicarbonate IV bolus  Repeat after 30-60 min if pH < 7.10
  • Treatment Progression • K: 8.2 • pH: 6.79 • LA: 15.2 17:00 • Insulin Regular 10 units + D50W x 4 • Calcium Gluconate 1 amp x 4 • Sodium Bicarbonate 8.4% 1 amp x 4 • Normal Saline 1L x 4 • Sodium Bicarbonate drip (3 amp in 0.45%NS) • Vancomycin 1 g + Zosyn 3.375 g IV In between… • K:8.6 • pH: 6.94 • LA: 16 18:30
  • Treatment Progression  No improvement in metabolic abnormalities despite medications administration  ICU team consulted  Emergency hemodialysis awaiting at ICU floor  During transportation patient developed Ventricular Tachycardia and rushed back to ED for CPR at 18:28
  • During the CPR…  Patient was shocked 3 times  Received Epinephrine 1 mg x 3  Amiodarone 300 mg IV push  100 mEq (2 ampules) of Na+ bicarbonate  No pulse  Patient was declared deceased at 18:47
  • Discussion Probable cause of death?
  • Rituximab Murine/human monoclonal anitbody FDA approved indications: •Chronic lymphoid leukemia (CLL) •Microscopic polyarteritis nodosa •Non-Hodgkin’s lymphoma (NHL) •Rheumatoid arthritis (RA) •Wegener’s granulomatosis Binds to the antigen CD20, located on pre-B and mature B lymphocytes CD20 is expressed on > 90% of B- cell NHL, but not expressed on normal plasma cells or normal tissue
  • Black Box Warning
  • Basis of Infusion Reaction
  • Possible Tumor Lysis Syndrome?  Lab values indicating TLS  K+: 8.2 mMol/L  SCr: 4.05 mg/dL  Ca2+: 7.3 mg/dL  No Uric Acid and Phosphate levels  Super acute onset  within hours  Similar case reports
  • Case Reports of Acute TLS Tumo r type Age (sex) WBC (x109) Immunotherapy Onset TLS (hours) Outcome CLL 26 (F) 112 Rituximab 375 mg/m2 24 Improved NHL 41 (M) Rituximab 375 mg/m2 6 Improved CLL 76 (M) 907 Rituximab 375 mg/m2 12 Expired HL 36 (M) ABVD 2 Improved
  • Conclusion  Infusion reaction to Rituximab  Cardiac arrest  Hyperkalemia  Acute kidney failure  Possible tumor lysis syndrome  More information needed to confirm TLS  Importance and timing of emergency hemodialysis
  • References 1. RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2012. Available at 2. Bicarbonate therapy in lactic aciosis. In UpToDate, Wiederkehr M., Emmett M. Oct 3, 2012. 3. Advanced cardiac life support (ACLS) in adults. In UpToDate, Pozner C. Feb 4, 2013. 4. Yang H., Rosove M., Figlin R. Tumor Lysis Syndrome Occurring After the Administration of Rituximab in Lymphoproliferative Disorders: High-Grade Non- Hodgkin’s Lymphoma and Chronic Lymphocytic Leukemia. Am J Hem. 1999; 62:247-250. 5. Davidson M, Thakkar S, Hix J et al. Pathophysiology, clinical consequences, and treatment of tumor lysis syndrome. Am J Med. 2004; 116:546-554. 6. McBride A, Westervelt P. Recognizing and managing the expanded risk of tumor lysis syndrome in hematologic and solid malignancies. J Hemtol and Oncol. 2012; 5: 75. 7. Suzuki T., Takeuchi M., Saeki H., et al. Super-acute onset of tumor lysis syndrome accompanied by hypercytokinemia during treatment of Hodgkin’s Lymphoma with ABVD chemotherapy. Clin Ther. 2010 Mar;32(3): 527-31.