NEW YORK—Overall, perioperative anaphylaxis is rare, and fatal instances are very rare, but it is common enough that most anesthesiologists will experience at least one case over a period of seven years, according to June Chan, MB, an assistant professor of anesthesiology at Weill Cornell Medical Center, in New York City. “If you haven’t seen it, you will,” Chan warned.
At the 2023 annual Postgraduate Assembly in Anesthesiology, Chan and Deirdre C. Kelleher, MD, also an assistant professor of anesthesiology at Weill Cornell, reviewed standards of care and clinical trends for perioperative anaphylaxis.
Culprits in Anaphylaxis
The most common triggers of perioperative anaphylaxis vary by geography: neuromuscular blockers in Europe, Australia and New Zealand, versus antibiotics in the United States and the United Kingdom. However, chlorohexidine is “increasing the incidence of anaphylaxis worldwide,” Chan said.
Although rocuronium is the neuromuscular blocker most likely to cause a reaction, this is probably related to how commonly it is used. Chan advised against the use of succinylcholine, which is actually twice as likely as other neuromuscular blockers to cause anaphylaxis.
“This means, if you have a patient with an allergic tendency, don’t give them succinylcholine. Actually, try to stay away from neuromuscular blockers in general if you’re not sure about previous anesthetic allergy,” she said.
As for reversal agents, Chan noted that the risk for anaphylaxis during emergence from anesthesia is changing as the use of sugammadex (Bridion) has increased in the United States.
Regarding antibiotics, cefazolin may have the same exposure problem as rocuronium, with its common use making it appear to be the antibiotic most likely to cause perioperative anaphylaxis.
The reason chlorhexidine is a growing cause of anaphylaxis is likely a matter of sensitization—as healthcare has eliminated latex from perioperative areas, chlorhexidine is now in nearly everything.
“It may be a little more difficult to diagnose. You’ll see patients who say they’ve had a rash with chlorhexidine and you don’t know whether it’s a type 4 reaction or a skin irritant reaction. Should we be limiting its use because we’re sensitizing our population? It’s such a good antibacterial agent I don’t think we’ll be decreasing its use, but it’s good to keep in mind as a possible trigger,” Chan said.
Presentation and Management
Hypotension is the defining symptom of perioperative anaphylaxis, present in all cases at some point, and reported as the first symptom in 46% of cases. Urticaria, although present at some point in 58% of cases, is the first symptom in only 3%, according to Chan.
“If you wait for urticaria to happen before you treat for anaphylaxis, you’re probably a little behind. Also, if you have very severe anaphylaxis and severe hypotension, urticaria is almost never present. So, urticaria is one of those symptoms that, while very specific, is not a sign you can use to rule out anaphylaxis simply because it is absent,” she said.
Perioperative anaphylaxis has been treated with epinephrine for many years now. However, currently “there is a strong hesitancy to use epinephrine and I’m not quite sure why. Part of it is that we’re not sure what dose to give,” Chan said.
Societies overseas have suggested initial doses of 10 to 100 mcg. In the United States, epinephrine commonly comes in two forms: 1 mg in 1 cc and 1 mg in 10 cc. Unfamiliarity with the amount of epinephrine in 1 cc may be one of the reasons many hesitate to administer it.
The second arm of treatment is fluids, which are often underadministered in anaphylaxis. “The mechanism here is massive extravasation. The key is to treat the acute hypotension—give epinephrine and fluids, but avoid colloids,” Chan said.
Epinephrine and fluids should take care of most moderate to severe anaphylaxis cases. However, if conditions do not improve after about 10 minutes, Chan recommends considering first- and second-line vasopressors, such as norepinephrine and vasopressin, in addition to glucagon for patients on beta blockers.
“Of course, you want to make sure you’ve excluded other conditions that may not be anaphylaxis and that you withdraw your triggers and think about the secret silent triggers like chlorhexidine and colloids,” she said.
Factors in Decision Making
Kelleher opened her talk by discussing how to address the 8% to 10% of patients who report a penicillin allergy. The first step is assessing whether the allergic reaction was real and is still relevant.
“They had a non-IgE [immunoglobulin E] reaction, maybe isolated pruritus, some gastrointestinal symptoms, a headache, a delayed reaction or the reaction was more than 10 years ago. Or they had a life-threatening reaction—blistering disorders, drug reaction with eosinophilia and systemic symptoms, nephritis—a situation where you’re obviously not going to give them cephalosporins,” she said.
Many people outgrow their allergy, with half losing penicillin sensitivity at five years and 80% at 10 years. “If a 60-year-old tells you they had a reaction when they were a baby, it’s probably safe to give them cephalosporins,” Kelleher said.
For patients who describe an IgE-mediated reaction, or a reaction less than 10 years ago, “we recommend sending the patient for allergy testing,” she said. If the patient tests positive, you can still cautiously administer cefazolin if the need is high due to their dissimilar R1 side chains. “If they test negative, you can rule out the penicillin allergy and update their chart.”
The chart update is important because unverified penicillin allergies are a public health concern. “Patients given an alternative to penicillin have a 50% higher risk for surgical site infections because the alternatives have poor gram-negative coverage,” Kelleher said.
Regarding patients who claim to be allergic to anesthesia, the most common allergy triggers are neuromuscular blockers, antibiotics and chlorhexidine, according to Chan. “Propofol allergy is far less common and the rates are likely overestimated,” Kelleher said. Typically, patients with a propofol allergy are allergic to one of the additives, such as ethylenediaminetetraacetic acid, so she recommends reading the label.
If, despite precautions, a patient does develop a reaction, she suggests administering epinephrine and fluids. If the reaction is mild, physicians should try to continue the procedure. However, for patients with severe hypotension in response to therapy, it remains a judgment call as to whether the surgery should proceed.
“The take-home points: antibiotics, neuromuscular blockers and chlorhexidine are your main culprits,” Kelleher said. “Many penicillin allergies can safely be delabeled by history alone, and you should develop an approach for the patient with an unknown or unclear allergy history because these patients are coming into our ORs every day.”
By Monica J. Smith
Chan and Kelleher reported no relevant financial disclosures.