anesthetic considerations for patients with narcolepsy

LESSON 13Volume 44*10/28/2021

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Anesthetic Considerations for Patients with Narcolepsy

Kathryn E. McGoldrick, MD, FCAI (Hon)Professor and Chair, Emerita

Department of AnesthesiologyAdvisory Dean for Student Affairs, Emerita

New York Medical CollegeValhalla, New York

Clinical Learning Environment Review (CLER)Department of Institutional Accreditation

Accreditation Council for Graduate Medical Education (ACGME)Chicago, Illinois

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167Curr Rev Nurs Anesth 44(13):165-176 2021

Anesthetic Considerations for Patients with Narcolepsy

Kathryn E. McGoldrick, MD, FCAI (Hon)Professor and Chair, EmeritaDepartment of Anesthesiology

Advisory Dean for Student Affairs, EmeritaNew York Medical College

Valhalla, New York

Clinical Learning Environment Review (CLER)Department of Institutional Accreditation

Accreditation Council for Graduate Medical Education (ACGME)Chicago, Illinois

LESSON OBJECTIVES

Upon completion of this lesson, the reader should be able to: 1. Define narcolepsy. 2. Discuss the epidemiology of narcolepsy. 3. Describe the symptoms and findings often associated with narcolepsy. 4. Enumerate the categories of drugs used to manage the symptoms of narcolepsy. 5. List the specific drugs administered to manage the symptoms of narcolepsy. 6. Articulate the circumstances that may contribute to the development of secondary narcolepsy. 7. Explain why obstructive sleep apnea may also occur in conjunction with narcolepsy. 8. Describe potential interactions between drugs administered to manage narcolepsy and anesthetic agents. 9. Formulate an anesthetic plan for a narcoleptic patient undergoing surgery who requires general anesthesia.10. Summarize ongoing research involving potential pharmacologic agents to mitigate narcolepsy.

IntroductionNarcolepsy is not as rare as one might imagine; it afflicts approximately 200,000 Americans, but fewer than 25% of those affected are properly di-agnosed. Under-diagnosis of narcolepsy is partly because its severity varies widely, and it can be mistaken for depression, epilepsy, the side effects of medications, and even laziness. The condition is as widespread as Parkinson disease or multiple sclerosis, and more prevalent than cystic fibrosis. Males and females are equally affected.

A long-term neurologic disorder characterized by an impaired ability to regulate sleep-awake cycles, narcolepsy is associated with excessive day-time sleepiness (EDS) and disordered regulation of

rapid eye movement (REM) sleep. The term nar-colepsie is from the French and was first coined in 1880 by Jean Baptiste Édouard Gélineau who used the Greek words narkē, meaning “numbness,” and lepsis, meaning “attack,” to describe the condition.

Narcolepsy is typically associated with one or more of the following conditions: cataplexy (sud-den partial or total muscle weakness without loss of consciousness, often precipitated by emotional stimuli such as anger, fear, or surprise), which can be mistaken for epileptic seizures; sleep paralysis (an ephemeral, generalized inability to move or speak during the transition from sleep to wakeful-ness); and/or hypnagogic and hypnopompic hal-lucinations (vivid, often frightening perceptual

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CNS Central nervous systemCSF Cerebrospinal fluidEDS Excessive daytime sleepinessFDA Food and Drug AdministrationGABA Gamma-aminobutyric acidGHB Gamma-hydroxybutyrateHLA Human leucocyte antigenMSLT Multiple sleep latency testNREM Non-rapid eye movement NRI Norepinephrine reuptake inhibitorOSA Obstructive sleep apneaPSG PolysomnographyREM Rapid eye movement SSRI Selective serotonin reuptake inhibitorTIVA Total intravenous anesthesia

Acronyms

Table 1Symptoms Sometimes

Associated with Narcolepsy

experiences occurring, respectively, immediately preceding sleep onset or following sleep termina-tion). Automatic behaviors can also occur whereby a person continues to function (e.g., talking, or-ganizing objects, etc.) during sleep episodes and awakens without any memory of having performed these activities. Approximately 20% of narcoleptics will experience all these symptoms (Table 1).

The etiology of narcolepsy is unknown, and can be multifactorial.

People with narcolepsy tend to sleep approxi-mately the same number of hours during a 24-hour cycle as people without the disorder, but the quality of sleep is poorer. Because narcoleptics are unable to experience the amount of restorative deep sleep that non-affected individuals do, narcoleptics live in a continuous state of sleep deprivation. More-over, narcoleptics are unique in that they enter into the REM stage of sleep at the initiation of sleep,

whereas those with normal sleep patterns experi-ence non-rapid eye movement sleep (NREM) for about 90 minutes before transitioning to REM sleep.

In as many as 10% of cases, there is a family history of the disorder. Often, those affected have diminished levels of the neuropeptide orexin (also known as hypocretin), which regulates appetite, wakefulness, and other cognitive and physiologic processes. Functional imaging studies have shown that narcolepsy is associated with abnormal hypo-thalamic functioning in the absence of consistent structural changes identifiable by contemporary imaging studies. The reduced levels of orexin may be secondary to an autoimmune condition. Trau-ma, infection, toxins, or psychologic stress may also be contributory to narcolepsy. Notably, case studies have reported the development of secondary narco-lepsy following neurosurgery adjacent to the hypo-thalamus or third or fourth ventricle in previously asymptomatic individuals. Surgical manipulation in the area of the hippocampus, pineal gland, and suprasellar areas has also been associated with new-onset narcolepsy.

Narcolepsy typically has its onset in adoles-cence and young adulthood. It often takes 15 years before onset and correct diagnosis occurs; this de-lay may exacerbate the disturbing features of the disorder. Because cognitive, educational, occupa-tional, and psychosocial problems are linked to the disorder, the condition can be especially devastat-ing to teenagers who are at a crucial time in their lives as they struggle to develop a healthy self-image, achieve academic and social success, and choose an occupation.

DiagnosisWhen all the symptoms of narcolepsy are appar-ent, the diagnosis is relatively straightforward. However, if the sleep attacks are isolated and cata-plexy is minimal or absent, diagnosis can be more challenging. The International Classification of Sleep Disorders requires that an individual experi-ence ≥3 months of EDS not explained by another cause, despite adequate nighttime sleep, to meet the criterion for a diagnosis of narcolepsy. Three tests that are frequently used to establish the di-agnosis of narcolepsy are polysomnography (PSG), the multiple sleep latency test (MSLT), and the Ep-worth Sleepiness Scale. When tested via PSG, peo-ple with narcolepsy fall asleep rapidly, enter REM sleep early, and may awaken frequently during the night. PSG is also valuable in identifying other possible sleep disorders that could cause daytime sleepiness, such as obstructive sleep apnea (OSA).

With the MSLT, the patient is given the op-portunity to sleep every two hours during normal

• Cataplexy• Sleepparalysis• Hypnagogichallucinations• Hypnopompichallucinations• Automaticbehaviors


wake times. After an overnight sleep study, the fol-lowing day the patient will be subjected to multiple tests where he or she will be instructed to nap after a full night’s sleep. Observations are then made of the time taken to attain various stages of sleep (sleep onset latency). MSLT is helpful in classify-ing narcolepsy into two subtypes. Narcolepsy type I is characterized by either cataplexy with a mean sleep latency of ≤8 minutes and/or ≥2 sleep-onset REM periods. Narcolepsy type II has the same MSLT parameters as type I, unaccompanied by cataplexy. Moreover, hypocretin levels in the ce-rebrospinal fluid (CSF) are low in narcolepsy type I but normal in type II. In addition, the primary genetic factor that has been heavily implicated in the development of narcolepsy involves a region of chromosome 6, known as the human leucocyte antigen (HLA) complex. Notably, an overwhelming majority of patients with narcolepsy in conjunction with cataplexy test positive for the HLA subtype DQB1*0602. This allele, however, is present in up to 40% of the adult American population and, hence, is non-specific for narcolepsy.

The Epworth Sleepiness Scale is a brief ques-tionnaire that is used to determine the probability of a sleep disorder, including narcolepsy, but is not specifically diagnostic of that condition. Finally, it is important to appreciate that narcolepsy may be associated with other comorbid conditions, such as asthma, depression, digestive system disorders, cardiac disease, hypercholesterolemia, hyperten-sion, panic disorder, and social anxiety disorder.

Treatment of NarcolepsyTreatment options are limited and consist mainly of oral medication and lifestyle changes. With re-gard to the latter, planned regular short naps can reduce the need for pharmacologic treatment of EDS, but the improvement in symptoms lasts only for a short duration. Although somewhat help-ful, daytime naps are not effective substitutes for nighttime sleep. In fact, there is a paucity of literature involving controlled double-blind studies of possible effective drugs, or other types of treatment, for narcolepsy.

Currently there is no cure for narcolepsy but the condition can be managed, with varying degrees of success.

The most common narcolepsy medications involve stimulant drugs for mitigation of EDS, including amphetamine and/or its derivatives, methylphenidate, pemoline, caffeine, and the wake-fulness-promoting agent modafinil. Another Food and Drug Administration (FDA)-approved treat-

ment option for narcolepsy is sodium oxybate, also known as sodium gamma-hydroxybutyrate (GHB). Initially developed as an anesthetic agent, the drug is a potent CNS depressant and should be adminis-tered exclusively during the nighttime to promote effective sleep. It can be used both for cataplexy associated with narcolepsy and for EDS. Sodium oxybate, a potential respiratory depressant, can trigger the development or exacerbate the severity of central apnea and OSA.

Tricyclic antidepressants such as clomipramine, imipramine, or protriptyline, tetracyclic antide-pressants, antipsychotic agents such as perphen-azine, and selective serotonin reuptake inhibitors (SSRIs) may be efficacious in controlling assorted symptoms of narcolepsy, such as cataplexy. An-other drug that is administered is atomoxetine, a non-stimulant and norepinephrine reuptake in-hibitor (NRI), which is purportedly devoid of addic-tion liability or recreational effects. Venlafaxine, an antidepressant that blocks the reuptake of both serotonin and norepinephrine, has shown promise in managing cataplexy but has notable side effects, which include sleep disruption (Table 2).

Research is ongoing to determine whether histamine-directed medications or gamma-aminobutyric acid (GABA)-directed medica-tions will be beneficial in the management of narcolepsy.

Specifically, it remains to be determined wheth-er H3 antagonists (e.g., pitolisant), which foster release of the wakefulness-promoting molecule amine histamine, will be useful in ameliorating symptoms of narcolepsy. Further, given the pos-sible role of hyperactive GABAA receptors in pri-

Table 2 Partial List of Drugs Currently Used

to Treat Narcolepsy Symptoms

• Amphetamineand amphetamine derivatives• Modafinil• Sodiumoxybate• Tricyclicantidepressants• Tetracyclicantidepressants• Selectiveserotoninreuptake inhibitors• Perphenazine• Atomoxetine• Venlafaxine


mary hypersomnia conditions such as narcolepsy and idiopathic hypersomnia, medications that could counteract this activity are being evaluated. These include clarithromycin and flumazenil. It is important to underscore that the positive effect of clarithromycin in primary hypersomnia is second-ary to its benzodiazepine antagonist-like effect, and not its antibiotic properties. Flumazenil, a GABAA receptor antagonist, is currently available only as an intravenous formulation. However, based on its pharmacologic properties, the drug is considered to have the potential be a promising agent for the treatment of primary hypersomnia.

The clinician should be knowledgeable about possible drug interactions between anesthesia medications and such stimulant medications as amphetamine, its derivatives, and methylpheni-date. These potent central nervous system (CNS) stimulants influence the release of endogenous catecholamines, such as norepinephrine and dopa-mine; hence, they function as indirect sympatho-mimetics. Reported complications related to their use in the perioperative setting include intracra-nial hypertension during a neurosurgical proce-dure in a patient with acute amphetamine abuse; downregulation of the sympathetic nervous system with chronic use, resulting in notable hypotension; and augmented requirements for induction agents. Further, it is important to appreciate that abrupt withdrawal of narcolepsy medications in patients with severe cataplexy symptoms can exacerbate symptoms for several hours and result in status cataplecticus.

Formulating an Anesthetic Plan for Patients with Narcolepsy

Prospective clinical trials in patients with narcolepsy are rare; most of the available litera-ture consists of case reports, observational studies, and retrospective reviews. Hence, currently there are no established guidelines or standards of care addressing the perioperative management of narco-leptics. Nonetheless, the Narcolepsy Perioperative Task Force, created by the Society of Anesthesia and Sleep Medicine, has established that evidence exists to suggest an increased perioperative risk for patients with narcolepsy.

In 2018, Hu et al published an excellent sys-tematic review that evaluated the current evidence regarding the perioperative outcomes and anes-thetic considerations for patients with narcolepsy. In 2019, a follow-up article by Hershner et al ad-dressing knowledge gaps in the perioperative man-agement of adults with narcolepsy and calling for further research was published. The recommenda-tions and conclusions listed below are derived from these vanguard publications.

Untoward events may include exacerbation of narcolepsy symptoms, as well as cardiopulmonary and other perioperative complications, including delayed emergence from anesthesia, erratic sensi-tivity to anesthetic agents, inadequate pain control, and possible intraoperative awareness. (There is an interesting report of a narcoleptic who required as long as 12 hours to emerge from general anes-thesia on three separate occasions). Cardiopulmo-nary complications most frequently manifest as hemodynamic instability, cardiac arrhythmias, and respiratory depression (Table 3).

Patients with narcolepsy may incur several types of perioperative adverse events that can be related to the disease itself, the effects of narcolepsy medications (and their interac-tions with anesthesia drugs), and medication withdrawal.

In general, narcolepsy medications should be continued preoperatively and throughout the peri-operative period, especially in patients with severe cataplexy; abrupt withdrawal can exacerbate symp-toms and even result in status cataplecticus. More-over, since cataplexy is precipitated by emotion, the stressful and emotional aspects of the surgical ex-perience can trigger and intensify cataplexy.

Given the potential for hemodynamic instability in patients taking stimulants, careful cardiovascu-lar monitoring is advised, and direct-acting vasoac-tive agents should be readily available intraopera-tively. The wakefulness-promoting agent modafinil may be associated with an increased risk of intra-operative awareness; bispectral index monitoring may be helpful in this setting.

A case-control study of 76 narcoleptic patients

Table 3Potential Perioperative Complications

in Patients with Narcolepsy

• Exacerbationofcataplexy• Hemodynamicperturbations• Alteredanestheticrequirements• Intraoperativeawareness• Respiratorycomplications including respiratory depression• Delayedemergence• Suboptimalpostoperative analgesia


reported that patients with narcolepsy had similar intraoperative courses as the matched controls, but narcoleptics experienced a higher rate of emergen-cy response team activation postoperatively due to hemodynamic instability and respiratory depres-sion. Interestingly, patients with narcolepsy had a greater prevalence of OSA than controls. Perhaps this is not surprising since orexin/hypocretin sig-naling plays a role in modulating upper airway pa-tency; reduced activity of orexinergic neurons may contribute to upper airway collapse during sleep, as seen in OSA. Moreover, approximately 35% of narcoleptics are obese, and 25% to 40% have OSA, which is an independent predictor of postoperative complications, including increased sensitivity to opioids and other sedative medications.

Obstetric patients may be at higher risk of worsening of their narcoleptic symptoms periop-eratively because frequently their medications are either reduced in dose or discontinued during preg-nancy (owing to concerns about deleterious effects on the fetus). These patients should be counseled about this possibility during pregnancy and during the postpartum period (in women who are breast feeding).

Reasonable, but not evidence-based, periop-erative management recommendations for narco-leptics might include (Table 4): 1) Continue nar-colepsy medications perioperatively; 2) Educate patients about potential exacerbation of narcolepsy symptoms; 3) Consider using a depth of anesthesia monitor; 4) Be knowledgeable about the pharma-cology of narcolepsy drugs; 5). Be prepared to man-age hemodynamic instability and postoperative

respiratory depression; 6) Consider the use of total intravenous anesthesia (TIVA), shorter-acting an-esthetic agents, and regional anesthesia when ap-propriate; 7) Use multimodal analgesia postopera-tively; 8) Be vigilant at all times, but especially in the postoperative period; 9) Advise against driving a motor vehicle in the immediate postoperative pe-riod; 10) Appreciate that neurosurgical procedures in the vicinity of the hypothalamus, as well as the third or fourth ventricle, may result in new-onset narcolepsy in a previously unaffected patient.

SummaryLiterature focusing on evidence-based recom-

mendations for perioperative management of pa-tients with narcolepsy is extremely sparse. This lesson attempted to summarize the current litera-ture, such as it is, pertaining to narcolepsy and its perioperative implications.

It behooves anesthesia providers to have a comprehensive knowledge of the pharmacology of agents used to treat narcolepsy and to consider potential drug interactions with our anesthetic agents in the perioperative period. Further, clini-cians must be aware that narcoleptics may be at greater risk of perioperative complications than those without the condition. Exacerbation of nar-colepsy symptoms as a consequence of the disease itself, associated dysautonomia and/or OSA, drug interactions, and drug withdrawal (when narcolep-sy medication is inappropriately discontinued) is a documented perioperative risk. Future research is needed to establish best practices for this vulner-able group of patients.

BibliographyAhmed I, Thorpy M., Clinical features, diagno-sis, and treatment of narcolepsy. Clin Chest Med 2010;31:371-381.

Andlauer O, Moore H, Jouhier L, et al. Nocturnal rapid eye movement sleep latency for identifying patients with narcolepsy/hypocretin deficiency. JAMA Neurology 2013;70:891-902.

Barateau L, Lopez R, Dauvilliers Y., Treatment op-tions for narcolepsy. CNS Drugs 2016;30:369-379.

Cavalcante AN, Hofer RE, Tippmann-Peikert M, et al. Perioperative risks of narcolepsy in patients un-dergoing general anesthesia: a case-control study. J Clin Anesth 2017;41:120-125.

Hershner S, Dauvilliers Y, Chung F, et al. Knowl-edge gaps in the perioperative management of

Table 4Perioperative Management

Recommendations

• Continuenarcolepsymedica- tions• Educatepatientsaboutpotential

narcolepsy exacerbation/complications• Considerintraoperativedepthof anesthesia monitoring• Bepreparedtomanagehemody- namic instability and postoperative respiratory depression• ConsideruseofTIVA,shorter- acting drugs, and regional anesthesia when appropriate• Multimodalanalgesia• Vigilancethroughouttheperiop- erative period


adults with narcolepsy: A call for further research. Anesth Analg 2019;129(1):204-211.

Hu S, Singh M, Wong J, et al. Anesthetic manage-ment of narcolepsy patients during surgery: A sys-tematic review. Anesth Analg 2018;126(1):233-246.

Mesa A, Diaz AP, Frosth M., Narcolepsy and anes-thesia. Anesthesiology 2000;92:1194-1196.

Ohayon MM., Narcolepsy is complicated by high medical and psychiatric comorbidities: A com-parison with the general population. Sleep Med 2013;14:488-492.

Scammell TE., Narcolepsy. N Engl J Med 2015;373:2654-2662.

Snow A, Gozal E, Malhotra A, et al. Severe hyper-somnolence after pituitary/hypothalamic surgery in adolescents: clinical characteristics and poten-tial mechanisms. Pediatrics 2002;110:e74.

Soltanifar S, Russell R.. Neuraxial anaesthesia for caesarean section in a patient with narcolepsy and cataplexy. Int J Obstet Anesth 2010;19:440-443.

Thorpy M, Zhao CG, Dauvilliers Y., Manage-ment of narcolepsy during pregnancy. Sleep Med 2013;14:367-376.

Thorpy MJ, Dauvilliers Y., Clinical and practical considerations in the pharmacologic management of narcolepsy. Sleep Med 2015;16:9-18.


Kathryn E. McGoldrick, MD, FCAI (Hon)

Dr. McGoldrick, a graduate of Dartmouth College and Cornell University Medical College, served for 15 years as Professor and Chair of Anesthesiology at New York Medical College, where she also was Residency Program Director and Advisory Dean for Medical Student Affairs. She was previ-ously on the faculty of Harvard Medical School and then Yale University School of Medicine. Cur-rently, she works full time for the Accreditation Council for Graduate Medical Education (ACGME) in the Department of Institutional Accreditation, focusing on the Clinical Learning Environment Review (CLER).

Dr. McGoldrick completed residency training in Anesthesiology at Brigham and Women’s Hospital in Boston, followed by subspecialty training in Pediatric Anesthesiology at Boston Children’s Hos-pital. She has authored more than 85 book chapters and more than 120 articles. Dr. McGoldrick also has authored or edited 17 books. She served from 2009 to 2013 on the Executive Committee of the International Association for Ambulatory Surgery (IAAS), and from 2005-2014 on the Board of the Foundation for Anesthesia Education and Research (FAER). Dr. McGoldrick has served as President of multiple organizations, including the Wood Library Museum of Anesthesiology, the Connecticut State Society of Anesthesiologists, the Society for Ambulatory Anesthesia (SAMBA), and The Academy of Anesthesiology. A member of Alpha Omega Alpha honor medical society, Dr. McGoldrick was the 2013 recipient of the SAMBA Distinguished Service Award (DSA), and in 2014 was awarded Honorary Fellowship in the College of Anaesthetists of Ireland. In 2017, she received the DSA of the Wood Library-Museum of Anesthesiology.

Dr. McGoldrick currently serves on the Board of the Anesthesia Foundation and is a Fellow of the New York Academy of Medicine. She was Chief Editor of Survey of Anesthesiology for 22 years, until 2017, and continues to serve on the Editorial Board of Current Reviews in Clinical Anesthesia®. Dr. McGoldrick delivered the Lewis H. Wright Memorial Lecture at the 2018 American Society of Anesthesiologists Annual Meeting in San Francisco, discussing “Airway Management through the Ages.” She also delivered the 2017 Ether Day Lecture at Massachusetts General Hospital/Harvard Medical School and the 2019 Allen I. Hyman Lecture on the History of Medicine and Anesthesiol-ogy at Columbia Presbyterian Hospital/Columbia University College of Physicians and Surgeons. Her interests outside medicine include travel, photography, volunteer work, and writing essays and poetry.


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• Narcolepsy, a long-term neurologic disorder, is characterized by an impaired ability to regulate sleep-awake cycles. Narcoleptics are at greater risk of perioperative complications.

• There is a greater incidence of OSA in narcoleptic patients; approximately 35% of narcoleptics are obese and 25% to 40% have OSA. They are, therefore, prone to the development of both central and obstructive apnea.

• Many of the drugs used to treat narcolepsy (e.g., amphetamines and SSRIs) can interact with drugs utilized in the perioperative period, and the potential for hemodynamic instability exists.

• Abrupt withdrawal of narcolepsy medications in patients with cataplexy symptoms can exacerbate these symptoms for hours and result in status cataplecticus.

• Narcoleptic patients may also have a higher incidence of intraoperative awareness; the wakefulness-promoting agent modafinil may be associated with an increased risk of intraoperative awareness and bispectral index monitoring is helpful in caring for these patients.

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POST-STUDY QUESTIONS

LESSON

MARK ALL ANSWERS ON BOTH THIS PAGE AND YOUR ANSWER CARD 13

1. People with narcolepsy: □ A. Sleep many fewer total hours than non- narcoleptics □ B. Have extreme difficulty falling asleep at night, experiencing prolonged sleep latency times □ C. May experience cataplexy □ D. Are usually diagnosed in the seventh decade of life

2. Narcolepsy may be associated with all of the following EXCEPT: □ A. Automatic behaviors during sleep □ B. Hypnagogic hallucinations □ C. Hypnopompic hallucinations □ D. Increased levels of orexin

3. The following statement about narcolepsy is TRUE: □ A. The etiology of the condition is well understood □ B. Secondary narcolepsy can occur following neurosurgery involving the hypothalamus or the third or fourth ventricles □ C. The disorder is typically associated with elevated levels of orexin □ D. Narcolepsy can be cured

4. Narcolepsy: □ A. Not uncommonly is associated with obstructive sleep apnea □ B. Is readily diagnosed in most affected individuals □ C. Is highly responsive to pharmacologic intervention, with marked and prolonged improvement in the disorder □ D. Has no perioperative implications for anesthesia providers

5. The following statement about narcolepsy is FALSE: □ A. There are two main subtypes of narcolepsy □ B. There is an abundance of literature involving controlled double-blind studies of effective drugs for treatment of narcolepsy □ C. Narcolepsy typically has its onset in adolescence and young adulthood □ D. Prolonged emergence from general anesthesia has been reported in some patients with narcolepsy

6. Recommendations for the anesthetic management of narcoleptic patients include: □ A. Continue narcolepsy medications □ B. Consider the use of intraoperative depth of anesthesia monitoring □ C. Be prepared to treat hemodynamic instability □ D. All of the above

7. The following statement about the chronic use of CNS stimulants to treat symptoms of narcolepsy is TRUE: □ A. They function as indirect sympathomimetics □ B. They result in down regulation of the sympathetic nervous system □ C. These drugs can be associated with an increased requirement for induction agents □ D. All of the above

8. Sodium oxybate: □ A. Is ineffective in treating cataplexy □ B. Is a tetracyclic antidepressant □ C. Is also known as sodium γ-hydroxybutyrate □ D. Is a respiratory stimulant

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anesthetic considerations for patients with narcolepsy

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