What is the management of an arsenic infusion reaction in a patient with a history of leukemia?

Management of Arsenic Infusion Reactions in Leukemia Patients

For arsenic trioxide infusion reactions in leukemia patients, immediately stop or slow the infusion based on severity grade, administer H1/H2 antihistamines (diphenhydramine 50 mg IV plus ranitidine 50 mg IV) and corticosteroids (methylprednisolone 1-2 mg/kg IV every 6 hours), and restart at 50% rate after symptom resolution for mild-moderate reactions, while permanently discontinuing for Grade 3-4 reactions. 1

Immediate Recognition and Initial Response

Stop the infusion immediately and assess the patient's airway, breathing, circulation, and level of consciousness. 1, 2 Early warning signs include patients feeling odd, uncomfortable, or expressing a need to urinate or defecate—these symptoms must be taken seriously with immediate blood pressure and pulse rate measurement. 1

• Maintain IV access with normal saline for medication administration and potential fluid resuscitation 3
• Position the patient appropriately: Trendelenburg for hypotension, sitting upright for respiratory distress, or recovery position if unconscious 1, 2
• Administer supplemental oxygen if needed 1, 4
• Call for medical assistance immediately 1, 2

Grade-Based Management Algorithm

Grade 1 Reactions (Mild)

• Slow the infusion rate to 50-60 mL/hour 1, 2
• Administer H1/H2 antihistamines: diphenhydramine 50 mg IV plus ranitidine 50 mg IV 1
• Monitor vital signs continuously 1
• Restart infusion at 50% of previous rate and titrate to tolerance once symptoms resolve 1, 2

Grade 2 Reactions (Moderate)

• Stop or temporarily cease the infusion 1
• Administer H1/H2 antihistamines: diphenhydramine 50 mg IV plus ranitidine 50 mg IV 1
• Give corticosteroids at a dose equivalent to 1-2 mg/kg IV methylprednisolone every 6 hours 1
• After symptom resolution, restart infusion at 50% rate and titrate to tolerance 1, 2

Grade 3-4 Reactions (Severe/Life-Threatening)

• Permanently stop the infusion 1, 2
• Administer epinephrine 0.3-0.5 mg (0.01 mg/kg, maximum 0.5 mL) intramuscularly into the lateral thigh if anaphylaxis criteria are met 1, 4
• Give H1/H2 antihistamines: diphenhydramine 50 mg IV plus ranitidine 50 mg IV 1
• Administer corticosteroids equivalent to 1-2 mg/kg IV methylprednisolone every 6 hours 1
• Rechallenge is strongly discouraged in severe reactions 1, 2

Management of Specific Complications

Hypotension

• Place patient in Trendelenburg position 1
• Administer fluid resuscitation with crystalloid bolus (1-2 L for adults) 4
• If hypotension persists despite epinephrine and fluids, use vasopressors: dopamine 400 mg in 500 mL at 2-20 μg/kg/min 1
• Alternative: vasopressin 25 units in 250 mL (0.1 U/mL) at 0.01-0.04 U/min 1

Bradycardia

• Administer atropine 600 μg IV 1

Patients on Beta-Blockers

• If refractory to epinephrine, administer glucagon 1-5 mg IV infusion over 5 minutes 1, 4
• This is critical as beta-blockers can blunt the response to epinephrine 4

Bronchospasm

• Administer albuterol nebulization 2.5-5 mg in 3 mL saline if unresponsive to epinephrine 4

Post-Reaction Monitoring

• Monitor vital signs continuously until complete resolution of symptoms 1
• Observe for at least 24 hours after severe reactions to detect biphasic reactions 1, 2
• For moderate reactions, observe for minimum 4-6 hours 2, 4
• Document the reaction grade, specific symptoms, timing of onset, and all treatments administered 1, 2

Critical Pitfalls to Avoid

• Never delay epinephrine administration if anaphylaxis is suspected—antihistamines and corticosteroids do not substitute for epinephrine in true anaphylaxis 2, 4
• Do not restart infusion at full rate after a reaction; always use 50% rate and titrate slowly 1, 2
• Do not discharge patients prematurely, especially those with airway involvement or requiring multiple interventions 2, 4
• Corticosteroids prevent biphasic reactions but provide no acute benefit—they are adjunctive therapy only 1, 4
• Do not attempt rechallenge in Grade 3-4 reactions as this significantly increases morbidity risk 1, 2

Special Considerations for Arsenic Trioxide

Arsenic trioxide is particularly effective for acute promyelocytic leukemia (APL) and is generally well-tolerated with appropriate monitoring. 5 The continuous slow-rate infusion method (18-20 hours daily at 8 drips/min) has been shown to have fewer toxic effects compared to standard 2-hour infusions. 6 However, hyperleukocytosis can occur and requires vigilant monitoring. 6