Using anesthesia records, we investigated whether propofol causes allergic reactions in patients with egg/soybean allergy. Propofol use was not significantly associated with a higher relative risk of allergic reactions in patients with egg/soybean allergy.
In this study, 0.8% of patients who underwent surgery involving anesthesiologists were allergic to egg/soybean (supplemental Table 1). In Japan, the prevalence of food allergy is reported to be 1–2% in all age groups. Approximately 35% of food allergies are reportedly caused by eggs and approximately 2% by soybeans, which is consistent with the prevalence found in this study [14].
Propofol contains soybean oil and egg yolk lecithin [4]. There is some controversy regarding the safety of administering propofol to patients with egg/soybean allergy. However, in recent years, many reports have indicated that propofol can be used safely in patients with food allergies [8, 15,16,17]. Egg yolk lecithin is not a major egg allergen, and allergic reactions to it are considered rare [18]. Regarding soybeans, propofol contains soybean oil, but soybean-derived proteins, which can cause allergies, have been removed. Therefore, there is no need to avoid propofol administration in patients with soybean allergy [15]. Indeed, our study supports the notion that, in Japanese clinical practice, propofol can be safely used in patients with egg/soybean allergy.
In our study, in patients who maintained anesthesia with inhaled anesthetics, thiopental was used as an induction agent more frequently than propofol in patients with egg/soybean allergy (supplemental Table 2). This finding suggested that some anesthesiologists tended not to use propofol in patients with egg/soybean allergy. However, the frequency of total intravenous anesthesia with propofol was not affected by the presence of a food allergy. This finding indicated that propofol was used in cases where the benefits of total intravenous anesthesia were obvious, such as in craniotomies [19], surgeries requiring motor-evoked potential monitoring [20], and in patients with a high risk for postoperative nausea and vomiting [21]. The factors used by anesthesiologists to decide whether to use propofol in patients with egg/soybean allergy are unclear. More cases need to be accumulated to determine these factors.
The frequency of allergy to propofol in patients with egg/soybean allergies in Japan is unclear. We assumed that more anesthesiologists would not administer propofol to patients with egg/soybean allergies if the frequency of allergic reactions to propofol was at least 10%. Therefore, the sample size in this study was calculated assuming a 10% frequency of allergic reactions to propofol in patients with a food allergy. We found that in the group of patients with egg/soybean allergy, the rate of allergic reactions to propofol was 1.32%, and the relative risk of allergic reactions after propofol use for patients with egg/soybean allergy was 1.14 (95% confidence interval, 0.10–12.4). On the basis of these results, we estimate that the actual frequency of allergic reactions is only a few percent when propofol is used in patients with food allergies. Clarification of the relative risk by accumulating and analyzing clinical use experiences is important in the future. The true relative risk would allow anesthesiologists to make better clinical decisions when selecting anesthetics for patients with egg/soybean allergies.
There are several limitations to this study. First, because this was a retrospective cohort study, there may have been unmeasured confounders or inherent biases. Severe asthma, atopic complications, or a history of anaphylaxis may have influenced the decision of anesthesiologists on whether to use propofol. Because of the nature of this study as a retrospective chart review analysis, investigation of the factors that individual anesthesiologists considered important in their choice of anesthetic agents was not possible. Second, this study is underpowered to determine the true relative risk of allergic reactions after propofol use compared with other anesthetics among patients with egg/soybean allergy. To examine whether propofol should be avoided clinically, the sample size is calculated assuming a 10% incidence of allergic reactions to propofol in patients with egg/soybean allergies. However, the observed incidence of allergy in the group of patients who used propofol was lower than estimated. Therefore, a large clinical study based on the incidence obtained in this study is needed to determine the true relative risk. Third, whether a patient has a food allergy is based solely on the patient’s declaration. Because antibody measurements and skin tests were not performed, there may have been cases in which food allergies had already resolved. However, by referring to self-reports and the food served during hospitalization, patients who reported having a food allergy were identified as those who routinely avoid particular food. Fourth, we did not consider the severity of egg/soybean allergy. Therefore, we cannot conclude whether the use of propofol for patients who previously experienced egg/soybean-induced anaphylaxis is safe. Fifth, minor allergic reactions that were not clinically problematic may have been overlooked. In this study, allergic reactions were identified by referring to the records of operating room nurses, ward nurses and surgeons, and those recorded by anesthesiologists. By referring to judgments made by more than one person, this should have prevented allergic reactions from being overlooked.
