22.4 Hypersensitivity Reactions and Extravasation

CPHON TCO V.G–H tests hypersensitivity reactions and extravasation as infusion emergencies. The chemotherapy chapter already named class toxicities and the first five minutes of a leak. The cellular-therapy and cytokine-release chapters already named interleukin-6 fever after CAR-T. This section is the chairside crash: stop the infusion, treat anaphylaxis as anaphylaxis, and manage a vesicant in tissue with a drug-class table, not a single folk-remedy temperature.

A 6-year-old who wheezes three minutes into pegaspargase, a 10-year-old who flushes and drops blood pressure during etoposide, a teenager on the fifth carboplatin cycle who develops delayed urticaria, and a 8-year-old whose peripheral vincristine site balloons are the CPHON pictures. ONCC uses generic drug names. Emergency drugs are at the bedside before the first drop.

Who reacts, and what you do in the first minute

High-yield triggers:

• Asparaginase products (pegaspargase, native Escherichia coli asparaginase). Hypersensitivity can be urticaria, bronchospasm, hypotension, or abdominal pain during or after the dose. After a true reaction, protocols often switch to an Erwinia-derived product such as crisantaspase. Silent inactivation is a therapeutic-drug-monitoring problem; this hour is the airway.
• Etoposide: both rate-related hypotension and true hypersensitivity. Slow a mild isolated pressure drop per protocol; treat anaphylaxis as anaphylaxis. Do not assume every etoposide blood-pressure dip is allergy, and do not assume every allergy is “just the rate.”
• Carboplatin (and sometimes cisplatin): reactions often appear after several cycles, not on dose one. A child who “always did fine” can still anaphylax on cycle five.
• Monoclonal antibodies (rituximab, dinutuximab, gemtuzumab, and others): infusion reactions and, less often, anaphylaxis. Premeds do not make epinephrine optional.
• Blood products: stop the unit, do not restart the same bag, notify the blood bank. Transfusion-associated circulatory overload and transfusion-related acute lung injury are other maps; widespread urticaria plus wheeze plus hypotension during a transfusion is still anaphylaxis until proven otherwise.

Stop the infusion. Keep the line with isotonic fluid. Call for help. Airway and oxygen. For anaphylaxis—urticaria or angioedema plus respiratory compromise or hypotension, or any rapidly progressing multi-system reaction—give intramuscular epinephrine in the anterolateral thigh as ordered, then antihistamine, corticosteroid, and isotonic fluids. Repeat epinephrine per protocol if the child is still shocked. Do not finish the bag. Do not give the first drug as an oral antihistamine while you “see if it settles.” Do not use a code-cart epinephrine infusion as an excuse to skip the intramuscular dose you can give now.

Mild isolated flushing without airway or blood-pressure change may be a rate decrease and notify per protocol. Restart only with an order. Desensitization is a formal, protocol-directed procedure in a monitored setting with emergency drugs drawn. It is not a floor-nurse experiment and not a “run it slower at home” plan.

IgE anaphylaxis is not cytokine release

Immunoglobulin E (IgE) anaphylaxis is minutes (sometimes up to an hour) during or just after an infusion: pruritus, urticaria, angioedema, wheeze, stridor, vomiting, hypotension. The first drug is intramuscular epinephrine.

Cytokine release syndrome (CRS) after CAR-T or blinatumomab starts hours to days later with fever first, then leak, hypoxia, and hypotension. Treatment is the CRS pathway: notify the cellular-therapy team, culture and cover infection, tocilizumab when criteria are met, careful fluids, steroids for refractory disease or ICANS. Epinephrine is not the automatic first CRS drug. Tocilizumab is not the automatic first anaphylaxis drug. A child who wheezes and breaks out in hives three minutes into pegaspargase is not “early CRS.” A child who spikes 39.4°C on day 4 after CAR-T without urticaria is not “late IgE.” If both could fit, treat the life threat in front of you and call both teams; do not delay epinephrine for true anaphylaxis while you debate interleukin numbers.

Dinutuximab pain and capillary leak are expected anti-GD2 toxicities from the immunotherapy chapter; they still do not cancel an anaphylaxis algorithm if the child has urticaria, stridor, and shock.

Extravasation: stop, aspirate, mark, class-specific next steps

Vesicants necrose tissue: anthracyclines (doxorubicin, daunorubicin), vinca alkaloids (vincristine, vinblastine), mechlorethamine, dactinomycin, and others on your unit’s list. Irritants inflame without the same necrotic punch; swelling still gets a stop-and-notify, not a shrug. The safe-handling chapter owns prevention culture and USP <800>; this chapter owns the injury.

If you suspect extravasation:

1. Stop the infusion immediately.
2. Aspirate residual drug through the existing catheter if you can; do not flush.
3. Disconnect tubing. Leave or remove the catheter per protocol after aspiration.
4. Mark the border and photograph per policy. Notify the provider and the extravasation/pharmacy pathway now.
5. Elevate the limb.
6. Apply cold or warm compresses by drug class using the current institutional or Oncology Nursing Society (ONS)–style vesicant table. Common teaching: vinca alkaloids often warm; anthracyclines often cold. That pairing is a table lookup, not a universal temperature you invent for every leak. Heat on an anthracycline and ice on a vinca are how nurses convert a small injury into a larger one.
7. Antidotes are protocol-directed. Commonly cited pairings: dexrazoxane (systemic) for anthracycline extravasation; hyaluronidase for vinca extravasation. Some anthracycline pathways also discuss topical dimethyl sulfoxide. There is no single universal antidote cream. Give what the protocol and the prescriber order, on the clock those documents use.

Prevention is cheaper than dexrazoxane. Give vesicants through a functional central line whenever policy allows. Confirm blood return before and during. Never force a flush. Stay with the child. Teach a child who can talk to report burning. A peripheral vesicant, when a protocol truly forces it, uses a fresh large-vein cannula and a nurse who does not walk away.

Walk the 6-year-old three minutes into pegaspargase: hives, wheeze, blood pressure falling. Stop, oxygen, intramuscular epinephrine, antihistamine, steroid, fluids. Do not complete the bag. Walk the 8-year-old whose peripheral vincristine burns and swells: stop, aspirate, do not flush, mark, photograph, elevate, warm compress if that is what the current vinca row of the table says, hyaluronidase as ordered. Walk the 11-year-old whose port doxorubicin infiltrates into the chest wall: stop, aspirate, cold if that is the anthracycline row, notify, dexrazoxane as ordered—not a warm pack because “heat helps all chemo.”

The CPHON product for TCO V.G–H is an infusion that stopped, an epinephrine syringe that reached the thigh, a CRS fever that was not mislabeled as allergy, a vesicant site that was marked and photographed, a compress temperature that came from the current table, and a central line that had blood return before the next vesicant ever hung.