Patients’ characteristics and the onset of the anaphylaxes
Case 1
A 29-year-old woman, ASA (PS) class 1, was scheduled to undergo uterine fibroid enucleation and right ovarian tumor enucleation under general anesthesia combined with epidural anesthesia. She had no history of allergies. After insertion of the epidural catheter, anesthesia was induced with fentanyl, remifentanil, propofol, and rocuronium, and the trachea was intubated. After administration of cefazolin 1 g before the start of surgery, blood pressure (BP) dropped to 50 mmHg or less, and did not respond to repeated bolus administration of ephedrine and phenylephrine, meanwhile heart rate (HR) increased rapidly from 50 to 90 beats/min, and arterial oxygen saturation of pulse oximetry (SpO2) decreased to 83%.
Case 2
A 69-year-old man, ASA (PS) class 3, was scheduled for retroperitoneoscopic prostatectomy for prostate cancer under combined general and epidural anesthesia. The patient had a history of rheumatoid arthritis, hypertension, hyperlipidemia, and endoscopic surgery for gastric cancer. He had a history of allergy to penicillin antibiotics. After placing an epidural catheter, anesthesia was induced using propofol and remifentanil. After administration of rocuronium, the trachea was intubated, and then cefotiam 1 g was administered. Before the start of surgery, the patient had persistent hypotension of systolic BP≤60 mmHg, which did not improve by repeated bolus administrations of ephedrine and phenylephrine. At the same time, HR rapidly increased from 40 to 70 beats/min. At the timing of starting surgery and feeding the retroperitoneal cavity with CO2 gas, SpO2 decreased to 92% at FIO2 0.4.
Cardiovascular and respiratory changes
Both patients had a HR increase accompanied by a progressive BP decrease. They also showed declines in both SpO2 at FI02 0.4 and EtCO2 under constant minute ventilation (MV). In case 1, EtCO2 decreased from 40 to 22 mmHg in association with an abrupt increase in the peak inspiratory pressure (PIP). Adrenaline (epinephrine) 50 μg, 75 μg were initially administered intravenously, in cases 1 and 2, respectively, and continuously given at 2 to 10 μg/min in both patients. Intravenous adrenaline immediately improved the refractory hypotension and increased EtCO2. In case 1, intravenous adrenaline also promptly reduced PIP. During the operating room stay, patients were infused 1750 and 1650 mL of crystalloid, respectively. Methylprednisolone 500 mg and chlorpheniramine 5 mg were also administered intravenously for both patients. Sugammadex was not used to treat anaphylaxis.
Cutaneous signs
None of the two patients had cutaneous signs at the onset of anaphylaxis. Facial flushing became apparent after the restoration of BP with adrenaline administration in both patients.
Serum tryptase and plasma histamine concentrations
Arterial blood was collected from the arterial lines to measure histamine and tryptase 30 to 40 min after the onset of anaphylaxis. The plasma histamine level was 23 ng/mL (normal range, 0.15 to 1.23 ng/mL) in case 1, and 1.34 ng/mL in case 2. In case 2, the total tryptase concentration was 3.4 μg/L (normal range, 1.2 to 5.7 μg/L).
Outcomes
Surgical operations were stopped and postponed in both cases 1 and 2. Patients were treated in the intensive care unit and discharged uneventfully.
Skin tests and reoperation
Patients were referred to dermatologists and underwent skin tests. Skin tests were performed 30 days after anaphylaxis for case 1, and 61 days for case 2. In cases 1 and 2, the antibiotics (cefazolin and cefotiam, respectively) and rocuronium had positive reactions in the intradermal test, although prick tests showed negative reactions. All other anesthetic agents used in each patient showed negative skin test reactivity. Reoperations were performed uneventfully on the 128th day after the anaphylaxis in case 1, and on the 181st day in case 2, while avoiding skin test-positive antibiotics and rocuronium.