An 8-year-old, 137-cm, 44-kg boy; + 2 standard deviations compared to average 8-year-old Japanese boys, diagnosed with autism was scheduled for the fourth cleft lip and palate surgery under general anesthesia at a dental hospital. The three general anesthesia procedures performed 8, 7, and 3 years prior had been uneventful. The third of those procedures was induced using sevoflurane, rocuronium, and fentanyl. Betamethasone was administered to prevent postoperative swelling, and piperacillin was administered as a prophylactic antibiotic. The fourth general anesthesia was induced using sevoflurane, propofol, rocuronium, fentanyl, and remifentanil, and betamethasone and piperacillin were again administered, as in the third cleft lip and palate surgery. Endotracheal intubation was uneventful; however, the patient developed elevated airway pressure 18 min after tracheal intubation, followed by systemic rash and hypotension with a systolic blood pressure of 64 mmHg. The patient was unable to ventilate by volume control ventilation at a maximum airway pressure of 30 cmH2O, and the anesthesiologists ventilated him manually with a maximum airway pressure of 70 cmH2O. Because perioperative anaphylaxis was suspected, the procedure was discontinued, and the patient was administered 0.2 mg of intramuscular adrenaline. Serum tryptase was elevated to 7.6 μg/L two hours after symptom onset compared to the level measured 19 h after the onset; 3.0 μg/L.

Four months after the event, the patient presented to the Department of Pediatrics of Fujita Health University Bantane Hospital, where an allergic workout was performed (approval number: HM23-458). Because the patient was afraid of multiple injections, we first performed a basophil activation test (BAT) for all drugs administered before the event and measured latex-specific IgE. Both tests yielded negative results. Next, we performed a skin prick test (SPT); however, the results were negative. In patients with symptoms in multiple organs, anaphylaxis cannot be excluded based on negative SPT and BAT results. Therefore, IDT was planned to identify the culprit drug, however, performing IDT was challenging. Although the patient tolerated the SPT, we assumed that multiple intradermal injections during IDT would be intolerable and potentially traumatic. Hence, we decided to perform IDT under general anesthesia in the operating room at Nagoya University Hospital.

Figure 1 shows the anesthetic chart for the IDT. General anesthesia was induced using sevoflurane and oxygen, and a peripheral venous catheter was inserted after topical disinfection using alcohol wipes. A supraglottic airway device (i-gel) was inserted uneventfully, and no skin symptoms, wheezing, or elevated airway pressure were observed. Spontaneous breathing was maintained throughout the test. All drugs other than piperacillin were diluted as described in previous guidelines [1, 2]. The maximum non-irritative concentration for piperacillin was set at 10 mg/mL. After confirming that the patient’s hemodynamics were stable, we initiated IDT. Saline and histamine were used as the negative and positive controls, respectively. The 1st IDT was performed using a tenfold dilution of the suggested maximum non-irritative concentration for IDT. The injection volume was 0.02 mL for all drugs, and a 3–5 mm wheal was created on the patient’s forearm. Wheal diameter was measured using a digital caliper at baseline (Wi) and 20 min after injection (W20). Test positivity was determined based on the following criterion: W20 ≥ Wi + 3 mm with surrounding flare [1].

Anesthetic chart for the intradermal tests. dBP, diastolic blood pressure; HR, heart rate; IDT, intradermal test; PV, peripheral venous catheter insertion; sBP, systolic blood pressure

Piperacillin (1 mg/mL) showed positive results (Fig. 2, Table 1). Considering the possibility of false negatives other than piperacillin, we performed a second IDT for all drugs at the suggested maximum non-irritative concentration. Piperacillin (10 mg/mL) again yielded positive results, whereas the other drugs yielded negative results (Fig. 3 and Table 1). The patient recovered from general anesthesia uneventfully, and we concluded that piperacillin was the causative agent. Subsequent surgery, using the same anesthetics and fosfomycin as the prophylactic antibiotic, was uneventful.

Results of the 1st intradermal test procedure

Results of the 2nd intradermal test procedure