A 62-year-old man (height and weight, 165 cm and 64.2 kg, respectively) had a glioma on the right side of his brainstem. He was alert but experienced left hemiparesis. He had untreated mild diabetes mellitus (hemoglobin A1c 6.3%), as well as mild hypertension for which he was prescribed an angiotensin II receptor antagonist (candesartan cilexetil, 4 mg once daily) and a Ca2+ channel blocker (amlodipine, 2 mg once daily). Surgical resection of the glioma under general anesthesia was planned, with neurological monitoring (motor and sensory evoked potentials) to determine the resectable margin of the tumor.
General anesthesia was induced via target-controlled infusion of propofol (4 μg/mL using a TERUMO infusion pump [TE-371; Terumo Corp. Ltd., Tokyo, Japan]) and continuous infusion of remifentanil (0.5 μg/kg/min), followed by administration of rocuronium (0.6 mg/kg). After tracheal intubation, anesthesia was maintained via target-controlled infusion of propofol (1.8–3.5 μg/mL) and continuous infusion of remifentanil (0.1–0.3 μg/kg/min). The bispectral index (BIS) was used to titrate the propofol dose and was maintained at 40–60 throughout the anesthesia. Fentanyl was injected intermittently for transitional analgesia (50–100 μg). The final fentanyl dose (100 μg) was administered more than 80 min before the end of the surgery, and the total fentanyl dose during the surgery was 500 μg. Neurological monitoring during the surgery was performed in the absence of a muscle relaxant.
During the surgery, there were no premature ventricular contractions (PVCs) or other arrhythmias, and the patient’s circulation and other vital signs were stable. The patient received an infusion of 1800 mL of a crystalloid solution, 1000 mL of a colloid solution (6% hydroxyethyl starch in normal saline), and 300 mL of 20% mannitol (total infusion volume 3100 mL) during the surgery. The blood loss was 865 mL, but the patient did not receive a blood transfusion.
After bony closure of the skull, 20 mL of ropivacaine 0.75% (2.34 mg/kg) was infiltrated around the wound edge. The operating time was 8 h and 42 min. At the end of the surgery, the propofol/remifentanil infusion was terminated. However, 30 min later, the patient had not regained consciousness or spontaneous breathing, even though the estimated blood concentrations of propofol and remifentanil were below subanesthetic levels. At that time, the BIS was approximately 70. The patient did not become hypothermic during surgery, and his core body temperature was above 37°C at the end of the procedure. Blood gas analysis revealed that the blood pH, oxygenation status, ventilation status, and electrolyte status were within normal levels (pH, 7.345; PaCO2, 40.7 torr; PaO2, 129.2 torr; HCO3
–, 21.7 mEq/L; base excess, -3.7; Na+, 140.6 mEq/L; K+, 3.58 mEq/L; and Ca2+, 1.168 mg/dL) under mandatory ventilation (FIO2, 0.4; VT, 500 mL; respiratory rate, 10/min). However, the PVC rate gradually increased to 15 beats/min. Taken together, these observations led us to suspect that LAST had occurred 40 min after ropivacaine infiltration and 30 min after propofol/remifentanil discontinuation.
We administered a 20% lipid emulsion (Intralipos®; Ohtsuka Pharmaceuticals, Inc., Tokushima, Japan) as a bolus of 150 mL, followed by continuous infusion at a rate of 10 mL/min (total volume 250 mL). After the bolus was administered, the PVCs disappeared, the blood pressure increased from 112/62 to 162/79 mmHg, the PR interval on ECG decreased from 0.16 to 0.12 s, and spontaneous breathing resumed. After the entire dose of emulsion was administered, the patient regained consciousness and responded to call stimuli, and the tracheal tube was removed. He was observed for 30 min in the operating room and then transferred to the post-anesthesia care unit in the neurosurgical ward.
To determine the total and free (protein-unbound) concentrations of ropivacaine, we collected 10 mL blood samples from the arterial line just before administering the lipid emulsion, 15 min after extubation (30 min after administering the lipid emulsion), and 11 h after administering the lipid emulsion. After sampling, the blood samples were centrifuged at 5000g for 5 min, and the supernatant (plasma) was stored at −80 °C until analysis. The total and free ropivacaine concentrations were determined via liquid chromatography/mass spectrometry according to previously reported methods [11, 12]. Both the total and free concentrations, and the free fraction ratio of ropivacaine, were higher in 30 min after lipid rescue than before lipid rescue (Fig. 1).