Narcolepsy, also known as Gélineau syndrome, is a chronic sleep disorder characterized by excessive sleepiness during the day, sleep paralysis, hypnagogic hallucinations and cataplexy (sudden loss of muscle tone). Common features are uncontrollable attacks of deep sleep and disturbed nocturnal sleep. We report the anaesthetic management for laparoscopic cholecystectomy of a patient with a long history of narcolepsy.
A 50-yr-old woman (92 kg, 172 cm) suffering from narcolepsy was scheduled for laparoscopic cholecystectomy under general anaesthesia. Narcolepsy was diagnosed 20 years ago, after evaluation in a sleep disorder centre. The daytime sleep attacks had a duration of 2-3 h and were characterized by uncomfortable sensation in the extremities, excessive sleepiness and sleep paralysis. She reported one attack about every 4 days. The patient was not receiving any medication for narcolepsy. She had received a general anaesthetic for a hysterectomy 13 years ago.
Preoperatively, a psychiatric evaluation confirmed no disturbance and the physical examination was unremarkable. A baseline EEG was recorded 24 h preoperatively, while the patient was sitting relaxed in a chair with her eyes closed. The EEG was normal, showing an alpha rhythm with peak frequency at 9 Hz. The patient was calm and very co-operative. She did not receive any premedication the night before surgery.
Before induction of anaesthesia, apart from routine monitoring (electrocardiography, heart rate, non-invasive blood pressure, SPO2), a BIS™ sensor was attached to the patient's forehead for connection to a BIS XP monitor (Aspect Medical Systems Inc., Newton, MA, USA). Also, an adult sensor (Somasensor®; Somanetics Corporation, Troy, MI, USA) connected to an INVOS 4100 cerebral oximeter (Somanetics Corporation, Troy, MI, USA) was attached to the skin over the right frontal area.
Anaesthesia was induced with thiopental 450 mg and cisatracurium 17 mg intravenously (i.v.). The patient received 3 μg kg−1 of fentanyl for intraoperative analgesia. Anaesthesia was maintained with sevoflurane in a nitrous oxide: oxygen mixture (FiO2: 0.4). Inhalational agent concentration was titrated according to bispectral index (BIS) values. At the end of the procedure, paracetamol 1200 mg and diclofenac 75 mg were administered intramuscularly for postoperative analgesia.
BIS and regional cerebral oxygenation (rRSO2) baseline values were recorded before induction of anaesthesia (BIS 98 and rRSO2 70%) and every 5 min thereafter. End-tidal sevoflurane concentration was titrated between 0.23% and 1.8% according to BIS. BIS values fluctuated between 40 and 60 and rRSO2 values between 68% and 76%. An EEG was recorded 24 h postoperatively and was normal without significant changes compared with the preoperative EEG. The postoperative course was uncomplicated and the patient was discharged on the third postoperative day. During her stay in the hospital, there was not any postanaesthetic change in the frequency and characteristics of her narcoleptic episodes.
Narcolepsy is an under-diagnosed neurologic disorder characterized by derangement of sleep-wakefulness cycle. The incidence of the syndrome internationally is estimated to be 0.02-0.16% . A genetic contribution via human leukocyte antigens DR2 and DQwl is possible. The alleles DQB1*0602 and DQA1*0102 have been strongly associated with the syndrome .
The disabling symptoms of the syndrome have a dramatic impact on patients' lifestyle and can lead to social isolation and depression. The pharmacological treatment is symptomatic and may be supplemented by behavioural strategies and psychological support. Central nervous system (CNS) stimulants (dextroamphetamine, methylamphetamine, methylphenidate, pemoline and modafinil) and antidepressants (tricyclics and selective serotonin reuptake inhibitors) have been used in narcolepsy . CNS stimulants are useful in reducing sleepiness, while antidepressants are effective in controlling cataplexy.
Due to the rarity of the syndrome, guidelines for the anaesthetic management of patients with narcolepsy have not been established. Our patient was not receiving any treatment. However, interactions of drugs to treat narcolepsy and anaesthetics are very likely. Amphetamines produce decreased sympathetic response to hypotension due to depletion of CNS catecholamine stores. Haemodynamic instability may occur intra- and postoperatively. Despite these possible complications, preoperative discontinuation of medication is under question. Burrow and colleagues  suggest that pharmacological therapy for narcolepsy should be continued perioperatively, since they found no increased risk for anaesthetic complications related to the narcolepsy medication. However, it all depends on the type of drugs used for narcolepsy treatment.
Prolonged recovery after general anaesthesia, postoperative hypersomnia and apnoeic episodes due to possible increased sensitivity to anaesthetic drugs may occur. On the other hand, regional anaesthesia may be an alternative choice. Unfortunately, narcoleptic fits have been reported during spinal anaesthesia and such an undesirable complication cannot be underestimated .
Oversedation can be prevented perhaps by avoiding benzodiazepines and using agents other than opioids for postoperative pain control . We avoided premedication and postoperative opioids. We also avoided the ultrashort-acting opioid remifentanil, which is associated with acute tolerance development and postoperative secondary hyperalgesia [7,8]. Tolerance development to the opioid receptors may decrease the efficacy of other opioids, which our patient might need postoperatively. Paracetamol and non-steroidal anti-inflammatory drugs offered adequate postoperative analgesia to the patient without sedative effects.
Propofol has been used uneventfully in anaesthetic management of narcoleptic patients . Total i.v. anaesthesia with short-acting agents such as propofol and remifentanil has been reported to be successfully used in a patient with narcolepsy who underwent cardiac surgery . The authors of that report considered that perioperative monitoring of the patient's hypnotic state would have added valuable information, but this kind of monitor was not available in their department .
There are limited data about inhalational anaesthesia in narcoleptic patients while there are no reports of using BIS and brain oximetry as adjuncts to the anaesthetic management of patients with narcolepsy. There is one case report in Spanish of using inhalational anaesthesia in Gélineau syndrome and the authors reported postoperative complications due to anaesthesia .
We used sevoflurane to maintain general anaesthesia. Although we do not know the impact of narcolepsy on BIS monitoring, we used BIS values to titrate the volatile anaesthetic agent, hoping to decrease our patient's anaesthetic requirements. We maintained BIS values between 40 and 60 in order to avoid either awareness or prolonged recovery. The surgical procedure lasted 95 min. After discontinuation of general anaesthesia, the BIS values increased from 62 to 97 over a period of 14 min. The patient recovered and was extubated safely. There were no postoperative undesirable events related to general anaesthesia.
Brain oximetry was also used for continuous monitoring of the regional cerebral oxygen saturation. We observed no significant changes in the intraoperative rRSO2 values as well as in the postoperative EEG when compared to the preoperative rRSO2 values and EEG.
For the management of this narcoleptic patient, we avoided preoperative benzodiazepines, kept opioid analgesics to a minimum and used inhalational anaesthesia with sevoflurane. The anaesthetic technique was uneventful. Since non-invasive brain monitoring is harmless and might provide some information, we used BIS and cerebral oximetry despite the lack of evidence-based data of this monitoring in narcolepsy.
1. Stanford University School of Medicine, Center for Narcolepsy. http://med.stanford.edu/school/Psychiatry/narcolepsy/symptoms.html
2. Mignot E, Lin L, Rogers W et al
. Complex HLA-DR and -DQ interactions confer risk of narcolepsy-cataplexy in three ethnic groups. Am J Hum Gen
3. Fry JM. Treatment modalities for narcolepsy. Neurology
(2 Suppl 1): S43-S48.
4. Borrow B, Burkle C, Warner DO, Chini EN. Postoperative outcome of patients with narcolepsy. A retrospective analysis. J Clin Anesth
5. Pasteau F, Graftieaux JP, Gomis P, Scavarda D, Leon A. Problems posed by spinal anesthesia in a patient with Gelineau disease. Ann Fr Anesth Reanim
6. Pelaez R, Hortal FJ, Bastida E, Barrio JM, Riesgo MJ. Narcolepsy and cardiac surgery: can anesthesia with propofol and remifentanil be safe? J Cardiothorac Vasc Anesth
7. Guignard B, Bossard AE, Coste C et al
. Acute opioid tolerance. Intraoperative remifentanil increases postoperative pain and morphine requirement. Anesthesiology
8. Joly V, Richebe P, Guignard B et al
. Remifentanil-induced postoperative hyperalgesia and its prevention with small-dose ketamine. Anesthesiology
9. Gómez-Garrido M, Torcal E, Novado E, Ibarra M, Cuesta J. Inhalation anesthesia in Gelineau syndrome (cataplexy-catalepsy). Rev Esp Anestesiol Reanim