What is the management for an untoward reaction during infusion?

Management of Infusion Reactions

Stop the infusion immediately, assess for anaphylaxis, and administer epinephrine 0.2-0.5 mg intramuscularly if anaphylaxis is suspected; for milder reactions, slow or temporarily stop the infusion and provide symptomatic treatment with antihistamines and corticosteroids. 1

Immediate Recognition and Initial Response

Stop the medication infusion immediately at the first sign of any untoward reaction, but maintain intravenous access with normal saline. 1, 2

Assess the patient systematically:

• Evaluate ABCs (Airway, Breathing, Circulation) and level of consciousness 1
• Position the patient appropriately: Trendelenburg position for hypotension, sitting upright for respiratory distress, or recovery position if unconscious 1
• Administer supplemental oxygen if needed 1
• Call for medical assistance immediately 1

Critical warning signs before reactions: Some patients report feeling "odd" or uncomfortable, or express a sudden need to urinate or defecate—these symptoms must be taken seriously with immediate vital sign assessment. 1

Determine Reaction Severity and Type

Anaphylaxis (Grade 3-4 Reaction)

Anaphylaxis requires immediate epinephrine administration:

• Epinephrine 0.2-0.5 mg (1 mg/mL) intramuscularly into the lateral thigh muscle 1
• Repeat every 5-15 minutes as needed 1
• Aggressive fluid resuscitation: 1-2 L normal saline IV at 5-10 mL/kg in the first 5 minutes, followed by crystalloid or colloid boluses of 20 mL/kg 1

Adjunctive medications for anaphylaxis:

• H1/H2 antihistamines: Diphenhydramine 50 mg IV plus ranitidine 50 mg IV 1
• Corticosteroids: Methylprednisolone 1-2 mg/kg IV every 6 hours (equivalent dose) 1
• Atropine 600 μg IV if bradycardia develops 1

For refractory hypotension despite epinephrine:

• Dopamine 400 mg in 500 mL at 2-20 μg/kg/min, titrated to response 1
• Vasopressin 25 U in 250 mL (0.1 U/mL) at 0.01-0.04 U/min 1
• Glucagon 1-5 mg IV over 5 minutes if patient is on beta-blockers 1

Cytokine Release Syndrome or Hypersensitivity Reaction (Grade 1-2)

Grade 1 (Mild):

• Slow the infusion rate 1
• Monitor vital signs closely 1

Grade 2 (Moderate):

• Stop or slow the infusion temporarily 1
• Diphenhydramine 50 mg IV plus ranitidine 50 mg IV 1
• Methylprednisolone 1-2 mg/kg IV every 6 hours 1
• Restart infusion at 50% rate and titrate to tolerance after symptom resolution 1

Grade 3-4 (Severe non-anaphylactic):

• Stop the infusion permanently 1
• Diphenhydramine 50 mg IV plus ranitidine 50 mg IV 1
• Methylprednisolone 1-2 mg/kg IV every 6 hours 1
• Rechallenge is discouraged in severe reactions 1

Drug-Specific Management Considerations

Monoclonal Antibodies

Cetuximab (90% reactions on first infusion):

• Requires premedication with corticosteroids plus antihistamines 1
• First dose should be given at slow infusion rate 1
• For Grade 3/4 reactions: stop infusion, aggressive symptomatic treatment, may resume at slower rate after resolution unless severe 1

Daratumumab (40-50% reactions, mostly on first infusion):

• Premedication with corticosteroids and H1/H2 antagonists recommended 1
• 82-95% of reactions occur on first infusion 1

PD-1/PD-L1 inhibitors (atezolizumab, durvalumab):

• Premedication NOT recommended 1, 3
• Incidence <1-2% 1
• For Grade 3/4: permanently discontinue 1

Chemotherapy Agents

Paclitaxel:

• Mandatory premedication: Dexamethasone IV plus diphenhydramine 50 mg IV plus H2 antagonist (ranitidine 50 mg or cimetidine 300 mg) 30 minutes before infusion 1
• Most reactions occur within first 10 minutes of first or second dose 1
• Despite premedication, 1-2% will have severe reactions—consider desensitization 1

Carboplatin/Oxaliplatin:

• No routine premedication recommended 1
• Reactions typically occur after 7-8 administrations 1
• For Grade 3/4: stop treatment, aggressive symptomatic therapy, consider desensitization 1

Docetaxel:

• Breast/NSCLC/gastric cancer: Oral dexamethasone 8 mg twice daily for 3 days starting 1 day before infusion 1
• Prostate cancer: Oral dexamethasone 8 mg at 12,3, and 1 hour before infusion 1

Post-Reaction Management

Monitoring requirements:

• Monitor vital signs continuously until complete resolution 1
• 24-hour observation recommended after severe reactions 1
• Corticosteroids help prevent biphasic reactions but are not critical for acute management 1

Documentation:

• Record specific symptoms, timing of onset, treatments administered 2
• Consider measuring tryptase levels 15 minutes to 3 hours after onset if anaphylaxis suspected 2
• Notify blood bank or pharmacy immediately for reporting systems 1

Rechallenge Considerations

Absolute contraindications to rechallenge:

• Anaphylaxis (Grade 4 reactions) 1
• Grade 3/4 reactions with PD-1/PD-L1 inhibitors 1

Possible rechallenge with premedication:

• Grade 1-2 reactions may tolerate rechallenge with premedication (antihistamines, corticosteroids, antipyretics) and slower infusion rates 4, 5
• Reduce infusion rate to 60-80 mL/h for subsequent infusions 5
• Consider desensitization protocols for platinum agents or taxanes with prior Grade 3/4 reactions 1

Common Pitfalls to Avoid

• Never delay epinephrine in suspected anaphylaxis—it is the only life-saving intervention 1, 2
• Do not use corticosteroids alone without antihistamines in acute reactions 2
• Avoid first-generation antihistamines (diphenhydramine) in mild reactions as they can worsen hypotension and tachycardia 2
• Do not confuse drug-specific requirements: cetuximab requires premedication while PD-L1 inhibitors do not 1, 3
• Corticosteroids are NOT effective for acute management—they only prevent biphasic reactions 1