Incidence of Intraoperative Hypersensitivity Reactions: What’s This About?

Saager et al.¹  used a methodology combining electronic search strategies and clinical adjudication to retrospectively determine the incidence of intraoperative hypersensitivity events in one U.S. surgical center. The authors concluded that the overall incidence of anaphylaxis was 1 in 4,583 surgeries, whereas that of hypersensitivity was 1 in 677. However, major methodologic issues should be highlighted, and the results must be debated because no conclusion can be effectively drawn from this study.

First, the claim that “the overall incidence of anaphylaxis was similar to that reported in previous studies but that of hypersensitivity reactions was nearly seven times higher”¹  is not accurate because this has not been proved. In addition, it is supposed that hypersensitivity was used to designate immediate hypersensitivity because delayed hypersensitivity does not arise during the perioperative period. Thus, six types of criteria were arbitrarily selected to identify potential perioperative hypersensitivity in 178,746 surgeries during the 7-yr study period. The adjudication committee further selected 264 cases of immediate hypersensitivity corresponding to 7% of the study population by 1, 2, 3, or 4 search criteria and subsequently classified these cases according to a modified Ring and Messmer scale. The search criteria included clinical features, biologic measurements, e.g., histamine, tryptase, or IgE (total or specific), and selected preferred terms. Some of these latter should not have been used because they are not consistent with immediate hypersensitivity. Particularly, the first-use syndrome has been described during hemodialysis² ; fixed eruption and drug dermatitis belong to cell-mediated hypersensitivity that has a delayed presentation³ ; and flushing, sensation of foreign body, and laryngospasm or stridor do not belong to perioperative immediate hypersensitivity per se.⁴  Therefore, it is unclear whether only clinical features related to perioperative immediate hypersensitivity⁴  were considered for including the 264 cases. In addition, the timing between the introduction of the suspected trigger and the onset of clinical features is lacking. Accordingly, the onset delay is a useful argument in the diagnostic approach of perioperative immediate hypersensitivity, which usually occurs within minutes, even 1 min, of anesthetic induction.⁴ 

Second, laboratory tests were performed in only five patients (1.7%) but unfortunately remained undetailed. One should keep in mind that tryptase increase is highly suggestive of mast cell activation as seen in anaphylaxis.^4–7  In contrast, total IgE has no indication in the diagnostic approach of perioperative immediate hypersensitivity,⁷  whereas the identification of serum IgE to quaternary ammonium provides possible evidence of IgE sensitization but does not prove that a neuromuscular-blocking agent elicited the immediate reaction per se.^4,6,8 

Third, skin testing was not performed, and thus, none of these 264 cases can be considered to be definitively supported by an appropriate allergologic assessment. The analysis of biologic and skin tests results should always be tied to a careful and complete review of the clinical history to identify the culprit agent and the pathophysiologic mechanism involved (allergic vs. nonallergic).^5–7 

Fourth, thus, we respectfully disagree with the authors who claim that “the use of neuromuscular blocking agents was not significantly associated with experiencing hypersensitivity reactions” because this has not been demonstrated. Neuromuscular-blocking agents and antibiotics (e.g., β-lactam drugs) still remain the main triggers involved in cases of perioperative anaphylaxis, whereas latex-induced allergy is now becoming less common.^4,9  Furthermore, only a few cases of anaphylaxis to hetastarch are reported worldwide,⁹  and this is not consistent with the statement that “high-molecular-weight hetastarch was significantly associated with hypersensitivity reactions.”

In conclusion, the methodology used by Saager et al.¹  is not suitable for evaluating perioperative immediate hypersensitivity because none of the 264 cases can be considered to be definitively supported by an appropriate allergologic assessment as recommended by the current guidelines.^5–7  In contrast, unfortunately, no conclusion can be drawn from this retrospective study.

Dr. Dewachter received payment for lectures, accommodations, and travel fees by MSD France (Courbevoie, France). The other author declares no competing interests.