A 73-year-old woman experienced anaphylaxis during her first rituximab infusion for mantle cell lymphoma. She developed severe hyperkalemia, lactic acidosis, and acute kidney injury. Despite aggressive treatment, her condition deteriorated and she went into cardiac arrest. She could not be resuscitated and her probable cause of death was hyperkalemia leading to cardiac arrest in the setting of acute kidney failure and possible tumor lysis syndrome given her underlying aggressive lymphoma and rapid clinical deterioration.

1. SEVERE INFUSION REACTION
TO RITUXIMAB
CASE REPORT
Hanna Yudchyts, Pharm D.
PGY-1 Pharmacy Resident
NSLIJ Lenox Hill Hospital

2. Objectives
 Introduce patient case
 Discuss metabolic abnormalities
 Hyperkalemia
 Lactic acidosis
 Learn about Rituximab
 Review infusion reaction
 Discuss possible Tumor Lysis Syndrome (TLS)

3. 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.

4. 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

5. 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

6. 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

7. 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

8. Metabolic Abnormalities

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

18. 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

19. Discussion
Probable cause of death?

20. 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

21. Black Box Warning

22. Basis of Infusion Reaction

23. 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

24. 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

25. 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

26. References
1. RITUXAN® (Rituximab) full prescribing information, Genentech, Inc., 2012.
Available at www.rituxan.com
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.