A 29-year-old man with a PTRF mutation (height 126 cm; weight 22 kg) was scheduled for mandibular dentigerous cystectomy. He was born with neonatal asphyxia and was diagnosed with non-Fukuyama muscular dystrophy at 4 months of age. At 3 years of age, he began treatment for nephrosis. By 19 years of age, he had experienced two syncopal episodes. Holter electrocardiography led to a diagnosis of LQTS, for which the patient was started on antiarrhythmic drugs. At 22 years of age, he was diagnosed using genetic analysis with a caveolin-related metabolic disorder caused by a PTRF mutation. By 29 years of age, he developed cholecystitis and visited our hospital. The cholecystitis was not clinically urgent, but a purulent dentigerous cyst extending to the bone was found that required treatment. The attending physician in charge of dental oral surgery requested assistance from the Department of Anesthesiology.
The patient’s primary symptoms were congenital generalized lipodystrophy associated with myopathy, LQTS, refractory nephrosis, abnormal lipid metabolism, and skeletal dysplasia (Figs. 1 and 2). He was taking methylprednisolone 4 mg/day, mexiletine 300 mg/day, propranolol 30 mg/day, levocarnitine 500 mg/day, alfacalcidol 1 μg/day, cyclosporine A 10 mg/day, and pravastatin 5 mg/day. We observed a generalized lack of subcutaneous fat on physical examination. Further, the patient reported that he was performing all his day-to-day activities without any assistance, and that he had no dietary restrictions.
Serum investigations revealed elevated levels of creatine kinase (282 U/L), total cholesterol (243 mg/dL), and triglycerides (272 mg/dL), as well as normal glucose level (91 mg/dL). Renal dysfunction was well controlled by medication, and his estimated glomerular filtration rate was within normal limits (275.5 mL/min/1.73 m2). A preoperative resting electrocardiograph showed a sinus rhythm, heart rate of 66 bpm, and a QT/QTc ratio of 370/383, which were normal. Cardiac function was also normal according to transthoracic echocardiography. Using a chest radiograph, we measured his narrowest tracheal diameter (14.5 mm) to select the size of the endotracheal tube. His pulmonary function tests showed a vital capacity of 1.92 L (69.8% of predicted) and a forced expiratory volume of 1.90 L (67.6% of predicted).
In planning anesthesia for this patient, we first considered avoiding volatile agents to prevent MH. Moreover, there were concerns about drug selection, given his abnormal lipid metabolism. We also required a plan in the event of a life-threatening arrhythmia due to LQTS. Furthermore, skeletal dysplasia may cause difficulty in securing the airway, and the use of a muscle relaxant was a concern due to his myopathy.
We opted for total intravenous anesthesia (TIVA) without using propofol, which has a high lipid content. We chose dexmedetomidine and midazolam as sedative drugs and remifentanil as an analgesic. A bispectral index (BIS™) monitor (MEDTRONIC, Minneapolis, MN, USA) was used to titrate each agent. We planned not to use muscle relaxant, but to handle a situation where administration of a muscle relaxant would be required, rocuronium was prepared, which could be reversed by sugammadex. We also planned to apply defibrillation pads throughout the 24-h perioperative period and had antiarrhythmic drugs ready for use in the event of a life-threatening arrhythmia. We prepared a McGrath® video laryngoscope for intubation. In case it did not fit, we had also prepared a pediatric Airway Scope® (PENTAX, Tokyo, Japan).
On the day of surgery, we first washed out volatile anesthetics from the anesthesia machine by flushing the system with oxygen (10 L/min for 30 min). We applied defibrillator pads soon after the patient entered the operating room due to his risk of developing a life-threatening arrhythmia. We also administrated atropine 0.01 mg/kg to avoid the occurrence of long QT due to bradycardia. The BIS score was 97 before the induction. Anesthesia was induced with continuous administration of dexmedetomidine 4 μg/kg/h for 15 min followed by midazolam 1−2 mg according to the BIS score and his vital signs. Lidocaine was sprayed around his larynx. The BIS score was 69 after when we administered midazolam up to 7 mg. After confirming that mask ventilation is possible, we administrated remifentanil 2 μg/kg/h and then performed laryngoscopy, but he had a strong gag reflex with 69 of the BIS. We then administered additional remifentanil (2 μg/kg), but the BIS score was still high (64) and he still had a gag reflex. Since we anticipated that administration of a large amount of remifentanil may cause extreme bradycardia, we decided to use a muscle relaxant instead of administering additional remifentanil. We administered an initial dose of rocuronium (5 mg), and an additional dose (5 mg), which helped relieve his gag reflex, and the BIS score decreased to 50. We placed an endotracheal tube (internal diameter 6 mm) using a McGrath® video laryngoscope without difficulty. Throughout the induction, there were no cardiovascular or oxygenation-related complications. For maintenance of anesthesia, the surgeon performed a mandibular nerve block using 1% lidocaine hydrochloride-epinephrine (9 mL), and we continued to titrate dexmedetomidine 0.7 μg/kg/h and remifentanil 0.15–0.25 μg/kg/min according to the invasiveness of the procedure, his BIS score, and his vital signs. Further, in order to avoid bradycardia, we did not administer additional remifentanil; however, this proved difficult because his BIS score remained high (60–80) during the surgery. We monitored his rectal temperature throughout the surgery, it was 35–36.5 °C throughout the surgery.
The surgery was completed in 34 min, with 51 mL of blood loss. Before extubation, we administered sugammadex and complete reversal of neuromuscular blockade was confirmed with a train-of-four (TOF) monitor (TOF-Watch®, MSD K.K. Kenilworth, NJ, USA). After the surgery was finished, his BIS score decreased and remained around 60 for more than 15 min. As the patient took longer than usual to regain consciousness, we used flumazenil to reverse the effects of midazolam. Soon after receiving flumazenil, his responsiveness and BIS score improved to 95, and he was extubated and transferred to the intensive care unit. Since the half-life of flumazenil is shorter than that of midazolam, we continued administering flumazenil for 3 h, reducing the dose by half every hour, to maintain consciousness and a BIS score > 90. Additionally, the defibrillation pads were retained until the next day. Despite using a non-standard anesthetic method and although the BIS score remained high during the surgery, the patient reported feeling comfortable and unaware during surgery at the next day post-operative visit. He was discharged without any complications.