General Anesthetic Management of a Patient With Kleine-Levin Syndrome

Abstract

Kleine-Levin syndrome (KLS) is a rare sleep disorder characterized by periodic hypersomnia and behavioral or cognitive disturbances. Although prolonged emergence from general anesthesia and postoperative hypersomnia may occur in a patient with KLS, there is little information about the safe anesthetic management of these patients. We describe the case of a 22-year-old female previously diagnosed with KLS who was scheduled to have her third molars extracted under general anesthesia. Because the patient had symptoms of periodic hypersomnia and hyperphagia, the surgery was scheduled during a KLS crisis interval. General anesthesia was induced with propofol, remifentanil, and rocuronium, and maintained with desflurane and remifentanil. To prevent overuse of anesthetic agents, an electroencephalogram (EEG)-based depth of anesthesia monitor (SedLine; Masimo Corporation) was used intraoperatively. A neuromuscular monitor was also used to carefully titrate use of a neuromuscular blocking agent. After surgery, sugammadex was administered, and the patient quickly emerged within 10 minutes, as also confirmed by the EEG monitor. She had no KLS recurrence postoperatively. When anesthetizing patients with KLS, an EEG-based depth of anesthesia monitor and neuromuscular monitor may be warranted to ensure complete emergence from general anesthesia. In addition, elective surgery should be planned during crises intervals.

Kleine-Levin syndrome (KLS) is a rare sleep disorder first described more than 90 years ago.^1,2 Its prevalence is estimated at 1 to 5 cases per million.³ KLS is characterized by recurrent episodes of hypersomnia, behavioral or cognitive disturbances like hyperphagia (rapid consumption of a large amount of food), and hypersexuality.⁴ Crises usually manifest at least once a year, ranging from 2 days to 4 weeks, during which patients with KLS can sleep ∼18 hours a day.⁵ In contrast, there are no symptoms during crisis intervals.⁴

When providing general anesthesia for patients with KLS, anesthesiologists should consider the possibilities of postoperative hypersomnia and prolonged or difficulty judging emergence from general anesthesia. However, little information is available about the general anesthetic management of patients with KLS. Here, we report the case of a patient with KLS scheduled for the extraction of multiple teeth under general anesthesia performed with the assistance of electroencephalogram (EEG)-based depth of anesthesia monitoring.

CASE PRESENTATION

A 22-year-old woman (height, 159 cm; weight, 63 kg; body mass index, 25 kg/m²) with a 9-year history of KLS and dental phobia was scheduled to undergo extraction of 4 third molars under general anesthesia. She reported taking no medications to treat her KLS and that her symptoms arose approximately once a month for 6 to 10 days in duration on average. During her KLS crises, she had typical symptoms including hypersomnia and hyperphagia. Her medical history was otherwise unremarkable with no reported allergies to foods or drugs. Routine preoperative blood and urine tests, electrocardiography, and pulmonary function tests were normal. She was admitted to the hospital and scheduled to undergo the planned dental procedure under general anesthesia during a crisis interval.

Upon admission, the patient demonstrated no specific symptoms of KLS. Sedative premedication was not prescribed or administered preoperatively the day of surgery. Upon arrival to the operating room (OR), standard American Society of Anesthesiologists (ASA) monitors were placed, and her preoperative vital signs were as follows: blood pressure 136/89 mm Hg, heart rate 67 beats/min, and oxygen saturation (SpO₂) 99%. In addition to the routine anesthetic monitoring, an EEG-based depth of anesthesia monitor (SedLine; Masimo Corporation) was applied to avoid excessive anesthetic depth and to confirm emergence from general anesthesia. A neuromuscular monitor was also applied to optimize and guide the use of nondepolarizing neuromuscular blockers throughout the case. After establishing peripheral venous access, general anesthesia was induced with propofol 100 mg, remifentanil continuous infusion 0.3 μg/kg/min, and rocuronium 36 mg, and nasal intubation with a cuffed preformed nasal endotracheal tube was successfully completed without any difficulties. Local anesthesia was administered via infiltration using 12 mL of 1% lidocaine with 1:200,000 epinephrine. General anesthesia was maintained desflurane 3.5% along with oxygen 1 L/min, air 3 L/min, and remifentanil continuous infusion 0.2 to 0.3 μg/kg/min. Patient Status Index (PSI) values obtained from SedLine monitor were kept between 32 and 45. The patient's vital signs were stable throughout the 38-minute operation. Acetaminophen 1000 mg was administered intravenously prior to concluding the case to reduce pain postoperatively. At the end of the surgery, sugammadex 120 mg was administered intravenously to ensure complete reversal of the rocuronium-induced neuromuscular blockade. The patient quickly emerged from general anesthesia with PSI values > 90 within 10 minutes following discontinuation of the maintenance agents. The total duration of general anesthesia was 89 minutes. Her recovery was uneventful with no symptoms of KLS postoperatively, and she was subsequently discharged on the fourth postoperative day.

DISCUSSION

According to the International Classification of Sleepiness Disorders, third version (ICSD-3), KLS is a sleep disorder characterized by recurrent episodes of hypersomnia that typically last from 2 days to 4 weeks and hyperphagia, usually with onset in early adolescence in males but occasionally in young adults and in women.³ Diagnostic criteria for KLS include recurrent episodes of hypersomnia and patients experiencing at least 1 of following symptoms during crises: (1) cognitive or mood disturbances (confusion, irritability, mutism, aggressiveness, derealization, hallucinations, and delusions); (2) hyperphagia with compulsive eating; (3) hypersexuality with inappropriate or odd behavior; and (4) abnormal behavior such as irritability, aggression, and odd behavior.⁶ In accordance with these diagnostic criteria, this patient was diagnosed with KLS when she was 13 years old, presenting with recurrent episodes of hypersomnia and hyperphagia lasting for 6 to 10 days.

This patient reported taking no medications to treat her KLS-related symptoms. Although several medications have been suggested for treating KLS, effective pharmacological therapy has not been established. For example, amantadine has been suggested for halting a KLS crisis, but long-term use of the drug may reduce its efficacy.⁴

The exact pathophysiology of KLS still remains unclear. It was reported that hypothalamic function, which contributes to the control of sleep and wakefulness, seems to be intact in patients with KLS.⁴ Although KLS is similar to narcolepsy in terms of central hypersomnia, there are apparent differences in their sleep patterns. Patients with narcolepsy have brief episodes of sleep,⁷ whereas patients with KLS sleep ∼12 to 24 hours a day during crises.⁸ Furthermore, cataplexy and sleep paralysis are found specifically with narcolepsy⁷ and not found with patients with KLS.⁸ In contrast, behavioral disturbances such as hyperphagia and hypersexuality are symptoms specific to KLS.⁸

Several triggering factors for inducing a KLS crisis have been reported such as infection, fever, alcohol consumption, head trauma, sleep deprivation, and stress.^8,9 In addition, the onset of KLS after surgery or general anesthesia has also been reported.^8,10,11 Therefore, it would be plausible that patients with KLS may have postoperative hypersomnia after general anesthesia. However, because of its rarity, there have been no recommendations for safe anesthetic management of patients with KLS.

A previous report was published regarding the prolonged recovery from general anesthesia and postoperative hypersomnia occurring in a narcoleptic patient.¹² Another report also suggested that avoiding sedative premedication and remaining vigilant for increased sensitivity to anesthetic agents were crucial for anesthetizing patients with narcolepsy.¹³ Accordingly, it is important to avoid excessive use of anesthetic agents when providing general anesthesia to patients with sleep disorders. In this case, sedative premedication was not utilized prior to the patient being transported to the OR. Because no information was available regarding the safest anesthetic agent for a patient with KLS, we chose desflurane, which can facilitate a faster emergence and recovery than other volatile inhalational anesthetics, and the ultra-short-acting opioid agonist remifentanil to ensure a rapid and complete emergence after surgery. In addition, other longer-acting opioid agonists like fentanyl were not chosen for postoperative pain management to avoid a slower emergence and recovery from general anesthesia, and acetaminophen was administered at the end of surgery instead.

Furthermore, we used the EEG-based depth of anesthesia monitor (SedLine) to guide intraoperative depth of anesthesia and prevent overuse of anesthetic agents. This monitor was used intraoperatively to assess brain function and quantify the depth of anesthesia (via PSI) by analyzing the spatial and temporal gradients of EEG frequency bands in the anterior-posterior dimension.¹⁴ It was generally accepted that PSI values should be maintained between 25 and 50 during general anesthesia, which we were able to do in this case. However, a limitation of using an EEG monitor for a patient with KLS is that EEG monitor cannot distinguish if a slow emergence from general anesthesia is attributed to anesthetic agents or a relapse/return of KLS symptoms.

Complete reversal of the nondepolarizing neuromuscular blocker (ie, rocuronium) was crucial to allow us to determine if any noted muscle weakness was caused by either residual muscle relaxant or sleepiness. Therefore, we used the neuromuscular monitor to guide and carefully titrate the rocuronium dosing and administered sugammadex to ensure complete reversal of the neuromuscular blockade. Fortunately, she quickly emerged from general anesthesia after the surgery and had no symptoms of KLS postoperatively.

Because this was an elective case, we could schedule her to undergo general anesthesia during an interval between her KLS crises. However, if general anesthesia was performed during a KLS crisis, it may have been difficult to judge her full emergence from general anesthesia. Therefore, it is important to perform elective surgery during a crisis interval, or choose local anesthesia, if possible. Moreover, consideration should be given to providing general anesthesia for patients with KLS in a hospital setting, especially if during an active crisis.

CONCLUSION

We successfully performed the general anesthetic management of a patient with KLS. Carefully conducted general anesthesia with desflurane and remifentanil likely represents an ideal choice for patients with KLS due to the rapid emergence and short recovery provided by these agents. Furthermore, use of an EEG-based depth of anesthesia monitor and a neuromuscular monitor are also helpful to ensure the complete emergence from general anesthesia. In addition, elective surgery requiring general anesthesia should ideally be planned during an interval between KLS crises.