Case 1
A 74-year-old male (height, 157 cm; weight, 78 kg) with no history of drug allergy was scheduled for a third debridement and skin grafting for a severe burn injury. He had a past medical history of hypertension and diabetes. The first debridement was performed one month before, and anesthesia was induced and maintained with remimazolam, propofol, ketamine, fentanyl, and rocuronium without any problems during the first surgery. The second debridement with tracheostomy was performed 9 days before, but the operation was discontinued because non-sustained ventricular tachycardia occurred due to the development of intraoperative hypothermia. Anesthesia was induced and maintained with propofol, ketamine, fentanyl, and rocuronium without any problems during the first surgery.
Before anesthetic induction for the third surgery, the patient’s vital signs were as follows: blood pressure, 162/64 mmHg; heart rate, 81 bpm; and SpO2, 94%. We connected a ventilator circuit to the tracheostomy tube without any problem. We induced anesthesia with 4 mg of remimazolam and 20 mg of ketamine. His systolic blood pressure quickly dropped to 30–40 mmHg, and SpO2 dropped to 73% without any S–T change in electrocardiography. Wheezing and any other abnormal respiratory sounds were not audible.
We administrated 100 μg of noradrenaline in multiple divided doses, but hemodynamics did not change drastically. We then administered 50 μg of intravenous adrenaline repeatedly (total 250 μg) and 2000 mL of crystalloid, and his blood pressure and SpO2 returned to 115/70 mmHg and 98%. At this point, we could not diagnose anaphylaxis because skin symptoms could not be confirmed due to the burn injury and there were no respiratory symptoms. We suspected that this severe hypotension was caused by hypovolemic and/or septic shock due to burn wound infection, which was emphasized by administration of anesthetics. Considering that the previous surgery had been canceled halfway, we decided to continue the surgery. Anesthesia was maintained with propofol, ketamine, and fentanyl with 0.03–0.2 μg/kg/min of continuous intravenous infusion of adrenaline during the surgery (Fig. 1).
The surgery was completed, and a subsequent blood test suggested that circulatory collapse after anesthetic induction was due to anaphylaxis. Serum tryptase level was elevated from baseline sample (2.9 μg/L) to acute sample (8.3 μg/L).
Case 2
A 59-year-old male (height, 176 cm; body weight, 52 kg) with no history of drug allergy was scheduled for a laparoscopic-assisted sigmoid colectomy. He had a past medical history of diabetes. He had undergone esophageal bypass surgery for cervical esophageal cancer and open liver biopsy. Anesthesia was induced and maintained with propofol, remifentanil, ketamine, and rocuronium during the previous surgery.
Before anesthetic induction, his vital signs were as follows: blood pressure, 124/84 mmHg; heart rate, 88 bpm; and SpO2, 99%. We induced anesthesia with 9 mg of remimazolam divided into three doses. The patient then complained of discomfort. Within a few minutes, he developed sinus tachycardia of 105 bpm, and we were unable to measure blood pressure with the manchette method due to hypotension and body movement. We were able to palpate the radial artery pulse slightly. Although the patient seemed to lose consciousness, the bispectral index was more than 90 and body movement continued. We administered 8 mg of ephedrine and intubated immediately after administration of 60 mg of propofol and 40 mg of suxamethonium. We catheterized the radial artery at the same time. Since the patient’s systolic blood pressure remained at 30–40 mmHg, ephedrine and phenylephrine were administered repeatedly, but hemodynamics did not change. Thus, we administered intravenous 50 μg of adrenaline repeatedly (total 300 μg), following which his blood pressure returned to 85/45 mmHg and hemodynamic was stabilized. After confirming hemodynamic stability, we started 2 mg/kg/h of continuous intravenous infusion of propofol for sedation.
At this point, we could not diagnose anaphylaxis because skin and respiratory symptoms could not be confirmed. We performed echocardiography, but no segmental asynergy, right ventricular dilatation, or inferior vena cava collapse was observed. Troponin T was not elevated (0.001 ng/mL). The operation was discontinued, and subsequent blood test suggested anaphylaxis. Serum tryptase was elevated from the baseline sample (4.1 μg/L) to the acute sample (7.8 μg/L). The time course of general anesthesia was shown in Fig. 2. We suspected remimazolam anaphylaxis considering the onset situation. However, the skin prick and intradermal tests were negative for remimazolam.
One month later, the operation was rescheduled, and anesthesia was induced and maintained with propofol, ketamine, fentanyl, and rocuronium. This operation was completed without any problems.