Culprits in Perioperative Allergy, With Kimberly Blumenthal, MD

Published on: July 22, 2026

Conference | Eastern Allergy Conference

In this Q&A following EAC 2026, Blumenthal discusses perioperative anaphylaxis risk stratification, hidden OR triggers, and penicillin allergy de-labeling.

Kimberly Blumenthal, MD, MSc, from Mayo Clinic, sat down with HCPLive following the Eastern Allergy Conference (EAC) 2026 to discuss her presentations on perioperative anaphylaxis and beta-lactam allergy. The conversation covered risk stratification for surgical patients with drug allergy labels, common and overlooked culprits behind intraoperative reactions, and how to counsel patients when a reaction's cause is never confirmed.

Blumenthal also discussed her second EAC 2026 topic, penicillin allergy delabeling, including who qualifies, how the evidence has shifted between skin testing and graded drug challenge, and when it still makes sense to keep an allergy label in the chart even after a negative workup.

Q&A: Culprits in Perioperative Allergy, With Kimberly Blumenthal, MD

HCPLive: How should clinicians risk-stratify patients with a suspected drug allergy ahead of surgery?

Blumenthal: Most surgeries happen in somebody who has at ≥ 1 drug allergy label, maybe a penicillin allergy history from childhood, or a pain medication like ibuprofen or an opiate. There are some labels that can interfere with care, so we want to know whether or not those allergies are real before they have the operation.

Drug allergy labels before surgery [are] important if they interfere with anesthesia. Also, since surgeries are painful, I think about pain medicines afterward. Do they have opioid allergies? Do they have NSAID allergies?

And then, [I think about] penicillin allergy and antibiotics. The most common antibiotics used are the beta-lactam antibiotics, and the most common single antibiotic in surgical prophylaxis today is cefazolin, or Ancef, a cephalosporin antibiotic.

A lot of people report a cephalosporin allergy, potentially from childhood. Since it's a beta-lactam, cross-reactivity is always a question if you had a penicillin allergy. But recent guidelines suggest there is no cross-reactivity between penicillin and cefazolin, so almost every patient with a penicillin allergy label can have cefazolin in the operating room.

[Drugs] with significant reactions you might want to avoid. [Drugs] that are lower or moderate risk, we could potentially test using a combination of skin testing and drug challenge tests.

What Are the Triggers of Perioperative Anaphylaxis?

HCPLive: What are the most common culprit agents in perioperative anaphylaxis, and how has that landscape shifted?

Blumenthal: The hardest thing is identifying the cause, because a lot of medications are given at once. We often rely on the anesthesia report, which dictates exactly when medications were administered and when the reaction started.

In the US, antibiotics are the most likely causative agent, usually cefazolin, the same medicine we want to use to prevent infections. Probably the closest second are the neuromuscular blocking agents, the agents we use to paralyze patients during surgery.

HCPLive: What are some of the underrecognized triggers?

Blumenthal: There are certain dyes used in surgery that can cause an allergy. Implantable devices might be coated in an antibiotic. Latex is another potential trigger.

And then the disinfectant. We clean the skin often with chlorhexidine gluconate, a very emerging cause of perioperative anaphylaxis, especially because patients are sometimes asked for multiple days beforehand to wash with it, and then they show up to the OR and get washed again. It's sensitization and then an allergic reaction in the operating room.

What To Do When Anaphylaxis Occurs in the Operating Room

HCPLive: What steps should an operating room team take when anaphylaxis occurs intraoperatively?

Blumenthal: It's the safest place to have anaphylaxis. These patients are either already intubated or can be intubated, so their airway can be protected, and they have multiple lines of IV access to administer medications. Epinephrine can be given, along with other vasopressors like norepinephrine, steroids, and antihistamines.

The hardest thing is recognizing that it's anaphylaxis, because the patient might be covered and there might not be a visible rash. Low blood pressure has a larger differential diagnosis, so not all low blood pressure is anaphylaxis. But once it's identified, it's a very safe environment to be treated, though it often does lead to rescheduling of that procedure.

HCPLive: For a patient who had perioperative anaphylaxis but no culprit was ever confirmed, how do you counsel them and their surgical team before a future operation?

Blumenthal: The best we can do is relay the results of all of our testing. If we had negative skin tests to a number of agents, it seems like that drug could be used again, and before the next surgery, we could start it with a test dose, giving a small amount first, watching the patient, then proceeding with the remainder.

The final thing we can do is suggest an alternative. Maybe we don't find a cause, but we think it might be the neuromuscular blocking agent, so we suggest using succinylcholine at the next surgery.

Is There an Ideal Candidate for Penicillin Allergy De-labeling?

HCPLive: Who is a good candidate for penicillin allergy delabeling, and how do you approach that conversation with patients?

Blumenthal: Everybody with a penicillin allergy label is a candidate for delabeling because the diagnosis is frequently missed. Even a rash last year to amoxicillin might have been due to the infection, not the drug. The more recent the allergy history, the more you should approach it as confirmatory testing or delabeling.

For the majority of my patients, who are older and talking about a reaction from childhood that their mother told them about, 50, 60, 70 years ago, the likelihood of true allergy is quite low; the immune system and penicillins have both changed since then.

When I approach that conversation, I explain that if they weren't allergic to penicillin, it opens up 17 different drugs without concern for an allergic reaction. Most patients are receptive, but those with significant reactions carry more fear and should be referred to an allergist.

Skin Testing vs Graded Challenge for Beta-Lactam Allergy Evaluation

HCPLive: How has the evidence evolved around skin testing versus graded challenge for beta-lactam allergy evaluation?

Blumenthal: In 2009 in the US, we got Pre-Pen back through the FDA, a product we can use for skin testing.2 When we were able to do more skin testing, we realized that in very low-risk people, the skin test isn't as good and produces false positives, so we should really be skin testing the higher-risk people.

At the same time, data came out showing direct challenge is safe in low-risk patients. The field has shifted: for lower-risk patients, direct drug challenge is the most effective way to safely remove the label, and for higher-risk patients, skin testing performs better.

When To Keep the Allergy Label

HCPLive: Are there situations where you'd recommend maintaining the allergy label even after a negative workup?

Blumenthal: Sometimes a patient requests it. I do a test and don't see an allergy, but the patient doesn't want to take penicillin again because overnight they had signs of an adverse effect, like a headache or a fever, something non-allergic. Then I discuss leaving it in the chart as an adverse effect, specifying it was headache only.

Another common scenario is patients feeling subjective itching without a rash. Itching alone is not an allergy, and I'd feel comfortable removing the label, but if the patient doesn't, I revise it to say “itching only,” not a full contraindication, to communicate to future doctors that I wasn't concerned about a significant reaction.

Watch the interview series with Kimberly Blumenthal, MD, here: What's Behind Perioperative Anaphylaxis? Cefazolin, Hidden Operating Room Allergens: Dyes, Implants, Chlorhexidine, Overwash, Most Penicillin Allergy Labels Are Wrong.

References

Blumenthal K. Perioperative Anaphylaxis. Eastern Allergy Conference. Accessed July 2026. https://easternallergyconference.org/
Magpantay G, Cardile AP, Madar CS, Hsue G, Belnap C. Antibiotic desensitization therapy in secondary syphilis and Listeria infection: case reports and review of desensitization therapy. Hawaii Med J. 2011;70(12):266-268.