Treatment of Rigors
The best treatment for rigors is meperidine 25-50 mg IV every 4 hours as needed, with the option to repeat within 30 minutes if rigors persist, or alternatively hydromorphone 0.5 mg IV every 15 minutes as needed (up to 3 total doses). 1
Primary Treatment Approach
Parenteral opioids are the mainstay of acute rigor management and should be administered promptly when rigors occur, as these symptoms can become severe and refractory, potentially leading to respiratory deterioration if not managed appropriately. 1
First-Line Pharmacologic Options:
- Meperidine (Demerol): 25 mg IV with option to repeat another dose within 30 minutes as needed for rigors (standard dosing 25-50 mg IV every 4 hours PRN) 1
- Hydromorphone (Dilaudid): 0.5 mg IV every 15 minutes as needed for rigors, may repeat up to 3 total doses 1
Prophylactic Measures
Prophylactic acetaminophen and NSAIDs should be administered to reduce severity and prevent escalation of rigors. 1
Recommended Prophylaxis:
- Acetaminophen: 650 mg PO every 4 hours scheduled (for fever above 100.5°F/38°C) 1
- Indomethacin: 50-75 mg every 6 hours or equivalent NSAID 1
- Important caveat: Stop NSAIDs if serum creatinine >2 mg/dL, decreased urine output, or platelets <50,000 x10^9/L 1
Context-Specific Considerations
In Infusion Reactions (Monoclonal Antibodies/Chemotherapy):
When rigors occur during infusion reactions, the management algorithm differs based on severity:
- Grade 1/2 rigors: Stop or slow the infusion rate, provide symptomatic treatment with the medications above, then restart infusion at half the rate once stable 1
- Grade 3/4 rigors: Stop the infusion immediately, provide aggressive symptomatic treatment including corticosteroids, and consider permanent discontinuation depending on the specific agent 1
In IL-2 Therapy (TIL Cell Therapy):
Chills and rigors alone are NOT indications to hold or discontinue IL-2 therapy. 1 These symptoms typically occur within 1-2 hours of each IL-2 dose and should be expected. 1
Role of Antihistamines
Pheniramine and other antihistamines are NOT recommended as primary treatment for rigors. While antihistamines like diphenhydramine (25-50 mg) are used as prophylaxis for infusion reactions in certain monoclonal antibody protocols 1, they are not the primary agents for treating active rigors once they occur. The evidence supports opioids as the definitive treatment for acute rigors. 1
When Antihistamines Are Used:
- Prophylaxis only: Diphenhydramine 25-50 mg IV or oral, or equivalent antihistamine, given before infusions of certain biologics (daratumumab, ofatumumab, rituximab) 1
- Not for acute rigor treatment: No guideline evidence supports pheniramine or other antihistamines as primary therapy for active rigors
Critical Monitoring
Preparation should be made beforehand so intervention is possible in a timely fashion. 1 Have medications readily available at bedside before anticipated rigor-inducing therapies.
Essential Assessments:
- Perform appropriate infectious workup and initiate antibiotics as warranted if fever accompanies rigors 1
- Monitor for respiratory deterioration, as severe refractory rigors can lead to other complications 1
- Ensure adequate IV access for rapid medication administration 1
Common Pitfalls to Avoid
- Do not rely on antihistamines alone for active rigor treatment—they lack efficacy for this indication and delay appropriate opioid therapy
- Do not continue NSAIDs in the setting of renal dysfunction, thrombocytopenia, or oliguria 1
- Do not delay opioid administration waiting for other interventions to work—rigors can escalate rapidly 1
- Do not assume rigors always require treatment discontinuation in IL-2 therapy, as they are expected and manageable with supportive care 1