Case 1
A 23-year-old, 169-cm, 53-kg male patient with jaw deformity was scheduled to undergo maxillary alveolar osteotomy. He had no history of allergy to any drugs or foods. Preoperative examination, including laboratory data, chest X-ray and electrocardiogram (ECG) were normal. No premedication was administered. After arriving at the operation room, arterial blood pressure (BP), heart rate (HR) and oxygen saturation (SpO2) were 152/85 mmHg, 71 bpm and 100%, respectively.
After venous access was obtained, 2 mg of midazolam (Dormicum; Astellas, Tokyo, Japan) and 50 μg of fentanyl (Daiichi Sankyo, Tokyo, Japan) were administered. Then, a nasogastric tube was inserted under sedation. At this time, the patient’s BP, HR and SpO2 were 147/82 mmHg, 67 bpm and 100%, respectively. Anesthesia was induced with a target controlled infusion (TCI) of 3 μg/ml of propofol (Diprivan; AstraZeneca K.K., Osaka, Japan) and 0.25 μg/kg/min of remifentanil (Ultiva; Janssen Pharmaceutical K.K., Tokyo, Japan). After mask ventilation with 100% oxygen, 40 mg of rocuronium (Eslax; MSD K.K., Tokyo, Japan) was administered to facilitate tracheal intubation. Nasotracheal intubation was performed uneventfully and confirmed by breath sound auscultation and capnography. Just after intubation, the remifentanil dose was decreased to 0.1 μg/kg/min.
A few minutes later, the anesthetist who was continuously listening to the respiratory sounds with a stethoscope suddenly noticed diminution of the respiratory sounds all over the patient’s chest 5 min after the administration of rocuronium. At this time, the patient’s lungs were manually ventilated. Although we do not have accurate data of peak inspiratory pressure (PIP) at that time, movement of the thoracic cage is limited with a PIP of ≥15–20 cm H2O. SpO2 was 99–100% throughout the event. Although we did consider the possibility of asthma, a beta-2 stimulant was not administered because wheezing was not identified. Although the trachea was suctioned and lungs were inflated again, the respiratory sounds did not improve. Four minutes after appearance of the respiratory symptoms, his BP dropped to 43/21 mmHg and HR was 89 bpm. Administration of 4 mg of ephedrine intravenously together with fluid therapy had no effect on the hypotension. As his BP and HR remained at 41/24 mmHg and 88 bpm respectively, administration of propofol and remifentanil were discontinued and an additional 4 mg of ephedrine was administered. Although the patient’s BP transiently increased to 69/33 mmHg (HR was 94 bpm), there was no further effect. Then, flushing of the skin over the chest and urticaria on the thigh emerged and spread widely all over the body over a few minutes. The time interval between emergence of the initial respiratory symptoms and appearance of skin manifestations was approximately 10 min.
According to the recommended treatment for anaphylaxis, 100% oxygen was supplied and 50 µg of adrenaline (Bosmin; Daiichi Sankyo), 5 mg of chlorpheniramine (Polaramine; MSD K.K.) and 500 mg of methylprednisolone (Solu-Medrol; Pfizer Japan, Tokyo, Japan) were administered. With this treatment, the patient’s BP and respiratory sounds gradually improved over several minutes and the systemic flush and urticaria disappeared approximately 30 min after their appearance.
Since rocuronium was strongly suspected as the allergen from the time course of events, remifentanil was carefully re-administered and sevoflurane was administered. Administration of rocuronium and other muscle relaxants was discontinued. Surgery was performed without any complications. Serum tryptase levels, which were measured approximately 30 min and 24 h after the administration of rocuronium, were 12.0 and 1.1 μg/l, respectively.
Case 2
A 21-year-old, 158-cm, 49-kg female patient with jaw deformity was scheduled to undergo maxillomandibular osteotomy. She had previously undergone palatoplasty under general anesthesia without any complications when she was 20 months old. She had no allergic history. Preoperative examination, including laboratory data, chest X-ray and ECG, was normal.
After sedation with 2 mg of midazolam and 50 μg of fentanyl, anesthesia was induced with 3 μg/ml of propofol (TCI) and 0.25 μg/kg/min of remifentanil. Nasotracheal intubation was successfully performed 2 min after 35 mg of rocuronium was administered. Anesthesia was maintained with 2–4 μg/ml of propofol and 0.1–0.3 μg/kg/min of remifentanil. For deliberate hypotension, 0.15 μg/kg/min of sodium nitroprusside (Nitopro; Maruishi Pharmaceutical Co. Ltd., Osaka, Japan) was continuously administered and BP was maintained at approximately 80/40 mmHg. Four hours after commencement of the surgery, the blood loss volume was approximately 350 ml, with more blood loss being anticipated. The patient’s BP and HR was 79/39 mmHg and 81 bpm, respectively. Hence, dextran 40 (Low Molecular Dextran L; Otsuka, Tokushima, Japan) was infused for replacement of the blood lost. Approximately 20 min after the start of dextran 40 infusion, the patient’s lungs suddenly became difficult to ventilate, and SpO2 decreased to 90%. After 100% oxygen was supplied and her lungs were adequately ventilated, SpO2 increased transiently to 98%. We asked the surgeons to stop the procedure and pulled off the drapes covering the patient. Lung sounds were difficult to hear on auscultation. However, evaluation revealed no problem with the endotracheal tube, and there were no skin manifestations that suggested anaphylaxis. Four minutes after appearance of the respiratory symptoms, the patient’s BP decreased to 60/20 mmHg and HR was 88 bpm. Hence, nitroprusside was discontinued and 0.2 mg of phenylephrine (Neo-Synesin; Kowa Pharmaceutical Co. Ltd., Nagoya, Japan) was administered. Fluid therapy was also administered. With these measures, although her BP transiently increased to 80/47 mmHg (HR was 87 bpm), it decreased once again to 61/42 mmHg (HR was 87 bpm) 10 min after the appearance of respiratory symptoms. Therefore, three additional 0.2 mg doses of phenylephrine were administered, and propofol and remifentanil were discontinued. Despite this, however, the hypotension did not improve. During the treatment of hypotension, SpO2 gradually decreased to 85%. Considering the possibility of tension pneumothorax, we commenced preparations for taking a chest X-ray. However, before we could do so, flushing of the skin and urticaria appeared on her thigh and spread widely over her entire body. The time interval from appearance of the first respiratory symptoms to that of skin manifestations was approximately 15 min.
According to the recommended treatment for anaphylaxis, 0.5 mg of adrenaline was administered intramuscularly, and 5 mg of chlorpheniramine and 500 mg of methylprednisolone were administered intravenously. Thereafter, ventilation and BP gradually improved over several minutes, and the systemic flush and urticaria disappeared approximately 30 min after their emergence. Anesthetics were re-administered and surgery was recommenced without any complications. In this patient, we considered dextran to be the offending allergen because of the time course of anaphylactic symptoms in relation to dextran administration. Postoperatively, the patient was transferred to the recovery room and sedated with midazolam and dexmedetomidine. She was successfully extubated the following day without any complications. Serum tryptase levels, which were measured approximately 30 min and 24 h after the administration of dextran 40, were 6.5 and 1.4 μg/l, respectively.