Act now

1. Stop the infusion and keep the IV line open with 0.9% saline. Don't flush more iron.
2. Assess airway, breathing and circulation immediately. Check BP, pulse, SpO2, and look for stridor, wheeze, hoarseness, tongue or lip swelling, urticaria, and hypotension.
3. If there is airway involvement, wheeze, hypotension, or swelling that is progressing, treat as anaphylaxis:
   • Give IM epinephrine 0.3 to 0.5 mg (1 mg/mL), repeated every 5 to 15 minutes if needed.
   • Give oxygen and IV fluids, and call for help or a rapid response.
   • Transfer to an acute care setting.
   • This is the textbook regimen (Goldman-Cecil Medicine, Intravenous Iron Therapy section).
4. For a milder reaction (hemodynamically stable, no airway signs), IV fluids (e.g., 500 mL saline) and IV corticosteroids (e.g., hydrocortisone) are used. Observe closely, because it can progress.
5. Avoid diphenhydramine premedication or treatment as a reflex. Goldman-Cecil states it can worsen symptoms in iron infusion reactions. It is not a substitute for epinephrine in anaphylaxis.

Which kind of reaction is it?

Background on iron sucrose

• Brenner and Rector's The Kidney says iron sucrose has an excellent safety record. It estimates life-threatening reactions at about 0.6 per million doses, versus 11.3 per million for high molecular weight iron dextran.
• The same text notes allergic reactions have been reported for all brands, and most mild events don't recur on rechallenge.
• The National Kidney Foundation Primer says iron sucrose has never been linked to a fatal anaphylactic reaction and needs no test dose.
• A test dose is not helpful for these non-allergic reactions (Goldman-Cecil Medicine).

After the event

• Observe until symptoms have fully resolved. Reactions can recur after improving, so monitor for several hours if the reaction was significant.
• Document the product, dose, rate and timing, along with the symptoms and treatment.
• Consider a serum tryptase drawn 1 to 3 hours after onset if anaphylaxis is suspected. This is my addition from general practice and not from the sources I retrieved.
• Report the event through your pharmacovigilance system.
• Future iron therapy: mild, resolved Fishbane-type reactions often allow a slower rechallenge with the same or a different IV iron. After a reaction with facial or airway involvement, get an allergy or hematology opinion before any further IV iron. Options include oral iron, or a different IV formulation given slowly under monitoring.
• Other causes of vomiting plus swelling, such as a food or drug allergen or an unrelated angioedema (including from ACE inhibitors), are worth considering if the timing doesn't fit.

Evidence check

What changes in pregnancy

• Use IM epinephrine 0.3 to 0.5 mg (1 mg/mL) in the anterolateral thigh. Repeat every 5 to 15 minutes as needed.
• In a systematic review of anaphylaxis in pregnancy (Carra 2021, PMID 34365055), 72% of the included articles proposed the same management as in non-pregnant patients, including epinephrine.
• Rosen's Emergency Medicine lists epinephrine as the preferred agent for anaphylaxis in pregnancy. It carries a theoretical uterine blood flow concern, which does not outweigh treating maternal shock.

• If the patient is in the second half of pregnancy (about 20 weeks or more), keep her in left lateral tilt (about 15 degrees) or manually displace the uterus to the left.
• This avoids aortocaval compression, which worsens hypotension.
• Do not sit her upright and let her stand. Raise her legs if she is hypotensive.

• Give high-flow oxygen. Pregnant patients have lower oxygen reserve and the fetus depends on maternal oxygenation.
• Give rapid IV crystalloid boluses if she is hypotensive.

• Use continuous maternal monitoring.
• If she is viable gestation (about 24 weeks or more), add continuous fetal heart monitoring once she is stabilized. Fetal heart rate changes can be the first sign of ongoing maternal compromise.
• Involve obstetrics early. Contractions and uterine irritability can occur during anaphylaxis. A 2021 systematic review (PMID 33181341) suggested beta-2 agonists may relieve severe anaphylactic uterine contractions better than epinephrine. I only saw the abstract-level conclusion, so treat this as a point to raise with obstetrics, not a protocol.

• If she is peri-arrest or arrests, follow maternal resuscitation protocols, which include left uterine displacement.
• At 20 weeks or more, consider early perimortem cesarean delivery. Call the obstetric team and anesthesia early.

Other considerations in pregnancy

• Vomiting is common in pregnancy, but with new facial swelling after an iron infusion, don't dismiss it as pregnancy-related.
• Corticosteroids such as hydrocortisone are acceptable for acute use. Antihistamines are adjuncts only. Remember Goldman-Cecil's caution that diphenhydramine can worsen iron infusion reaction symptoms.
• Product and timing: the Goodman & Gilman table notes some IV iron products are avoided in pregnancy, but iron sucrose is the formulation most commonly used in pregnancy (Creasy & Resnik's Maternal-Fetal Medicine, Iron Deficiency Anemia). IV iron is generally avoided in the first trimester. What is the gestational age? I can tailor the advice to it.
• Safety data: a meta-analysis of 11 trials in pregnant patients with iron deficiency anemia, mostly iron sucrose, found no hypersensitivity reactions. That does not exclude a reaction in this patient.
• Epidemiology: anaphylaxis in pregnancy is rare, at about 1.5 to 3.8 per 100,000 pregnancies. Most cases are from beta-lactams, latex and anesthetic agents. Iron is not a typical cause, so also consider other triggers given at the same time.

Afterward

• Observe longer than usual and keep obstetric review going. Do a fetal assessment (CTG or ultrasound as gestation allows) even if she looks recovered.
• Document the reaction clearly, including the product and gestational age.
• Refer to allergy or hematology before any future IV iron. Oral iron remains the usual alternative for pregnancy anemia. Creasy & Resnik's notes ferrous sulfate 325 mg one to three times daily, or the WHO dose of 60 mg elemental iron daily, with the GI side effects dose-dependent.

Evidence check