Respiratory Physiology DuringSleep

Vipin Malik, MD*, Daniel Smith, MD,Teofilo Lee-Chiong Jr, MD

KEYWORDS

� Ventilatory regulation � Respiratory motoneurons � Hypoxemia � Hypercapnia� Pneumotaxic center � Apneustic center � Chemoreceptors

KEY POINTS

� Ventilatory regulation is conceptually best understood as a 3-part system consisting of a centralcontroller, sensors, and effectors.

� The effectors of respiration include the respiratory motoneurons and muscles, which are involved ininspiration and expiration.

� Positional changes during sleep (ie, nonupright position) affect the mechanics of breathingsignificantly.

� Both hypoxemia and hypercapnia can develop during sleep in patients with chronic obstructivepulmonary disease.

� Upper-airway narrowing and excess weight, if present, can increase the mechanical load on therespiratory system as well as breathing work.

The respiratory system provides continuoushomeostasis of partial pressures of arterial oxygen(PaO2), carbon dioxide (PCO2), and pH levels duringconstantly changing physiologic conditions. Thiselegant system responds promptly to subtle varia-tions in metabolism occurring in both health anddisease. During wakefulness, volitional influencescan override this automatic control. Modificationsoccur in the regulation and control of respirationwith the onset of sleep. Furthermore, thesechanges differ significantly with specific sleepstages. These alterations in respiratory controlcan result in the pathogenesis of sleep-relatedbreathing disorders and limit the usual respiratorycompensatory changes to specific disease states.This article reviews the normal physiology of respi-ration in both awake and sleep states, anddiscusses the effects of common diseaseprocesses and medications on the respiratoryphysiology of sleep.

A version of this article originally appeared in Sleep MeSection of Sleep Medicine, National Jewish Medical and* Corresponding author. Section of Sleep Medicine, DiviJewish Health, 1400 Jackson Street, M323, Denver, CO 80E-mail address: malikv@njhealth.org

Sleep Med Clin 7 (2012) 497–505http://dx.doi.org/10.1016/j.jsmc.2012.06.0111556-407X/12/$ – see front matter � 2012 Published by E

CONTROL OF RESPIRATION

Ventilatory regulation is conceptually best under-stood as a 3-part system consisting of a centralcontroller, sensors, and effectors. Sensors primarilyinclude central and peripheral chemoreceptors,vagal pulmonary sensors, and chest-wall and respi-ratory muscle afferents. Data from these sensorsregarding dynamic oxygen and CO2 levels, lungvolumes, and respiratory muscle activity are contin-uously transmitted to the central controller. Withinthemedulla, thecentral controllergeneratesanauto-mated rhythm of respiration that is constantly modi-fied in response to an integrated input from thevarious receptors. The controller modulates motoroutput from the brainstem to influence the activityof the effectors, namely respiratory motoneuronsand muscles. These effectors then alter minuteventilation and gas exchange accordingly (Table 1).

The medullary ventilatory center consists ofneurons in the dorsal respiratory group (DRG)

dicine Clinics Volume 5, Issue 2.Research Center, Denver, CO, USAsion of Critical Care and Hospital Medicine, National206.

lsevier Inc. sleep.theclinics.com

Table 1Control of respiration

Controllers/Effectors Location Afferents Effects

Dorsal Respiratory group Dorsomedial medulla, ventrolateral tothe solitary tract

Upper airways, intra-arterialchemoreceptors, and lung afferentsvia the 5th, 9th and 10th cranial nerves,respectively

Increased frequency of a rampingpattern of firing during continuedinspiration

Ventral Respiratory Group Ventrolateral medulla Response to the need for forcedexpiration occurring during exerciseor with increased airways resistance

Respiratory effectors muscles areinnervated from the VRG via phrenic,intercostal and abdominalmotoneurons.

Pneumotaxic center Rostral pons consists of the nucleusparabrachialis and the Kolliker-Fusenucleus.

Pontine input serves to fine tunerespiratory patterns and mayadditionally modulate responses tohypercapnia, hypoxia, and lunginflation

Duration of inspiration and providetonic input to respiratory patterngenerator

Apneustic center Lower pons Pneumotaxic center and vagal input Provide signals that smoothly terminateinspiratory efforts

Central Chemoreceptors Ventrolateral surface of medulla Extracellular fluid [H+] concentration Respond to changes in brainextracellular fluid [H+] concentration

Peripheral Chemoreceptors Carotid bodies and the aortic bodies Afferent input to the medulla throughthe 9th cranial nerve

Respond mainly to PaO2, but also tochanges in PaCO2 and pH

Pulmonary Mechanoreceptors 1. PSRs are located in proximal airwaysmooth muscles.

2. J-receptors are located in thejuxtacapillary area and appear tomediate dyspnea in the setting ofpulmonary vascular congestion

3. Bronchial c-fibers

1. Respond to inflation, especially in thesetting of hyperinflation

2. Mediate dyspnea in the setting ofpulmonary vascular congestion

3. Affect bronchomotor tone andrespond to pulmonary inflammation

Malik

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and the ventral respiratory group (VRG) (Fig. 1).1

Located in the dorsomedial medulla, ventrolateralto the solitary tract, the DRG was previouslybelieved to be the site of rhythmic inspiratory drive.More recent research in animal models suggeststhat the respiratory rhythm is generated by a groupof cells known as the pre-Botzinger complex,a network of cells surrounding the Botzinger com-plex in the ventrolateral medulla.2

The medullary centers respond to direct influ-ences from the upper airways, intra-arterial chemo-receptors, and lung afferents via the fifth, ninthand tenth cranial nerves, respectively. The DRG

Fig. 1. A simplified diagram of the principal efferent (leftsection through the brain, brain stem, and spinal cord isshading), as are the central nervous system links withhttp://www.netterimages.com. � Elsevier Inc. All rights re

appears to be active primarily during inspiration,with increased frequency of a ramping pattern offiring during continued inspiration. The VRG,located within the ventrolateral medulla, containsboth inspiratory and expiratory neurons. VRGoutput increases in response to the need for forcedexpiration occurring during exercise or withincreased airways resistance. Respiratory effec-tors muscles are innervated from the VRG viaphrenic, intercostal, and abdominal motoneurons.

Poorly understood pontine influences furtherregulate and coordinate inspiratory and expiratorycontrol. The pneumotaxic center in the rostral

) and afferent (right) respiratory control pathways. Ashown (with pertinent respiratory areas indicated bythe respiratory apparatus. (Netter illustration fromserved.)

Malik et al500

pons consists of the nucleus parabrachialis andthe Kolliker-Fuse nucleus. This area appears toprimarily influence the duration of inspiration andprovide tonic input to respiratory pattern genera-tors. Similarly, the apneustic center, located inthe lower pons, functions to provide signals thatsmoothly terminate inspiratory efforts. The pontineinput serves to fine-tune respiratory patterns andmay additionally modulate responses to hyper-capnia, hypoxia, and lung inflation.3 The automaticcentral control of respiration may be influencedand temporarily overridden by volitional controlfrom the cerebral cortex for a variety of activities,such as speech, singing, laughing, intentionaland psychogenic alterations of respiration, andbreath holding.Afferent input to the central controllers is

mediated primarily by central chemoreceptors,peripheral chemoreceptors, intrapulmonary re-ceptors, and chest-wall/mechanoreceptors. Che-moreceptors provide a direct feedback to centralcontrollers in response to the consequences ofaltered respiratory efforts. Central chemorecep-tors, located primarily within the ventrolateralsurface of medulla, respond to changes in brainextracellular fluid [H1] concentration. Otherreceptors have been recently identified in thebrainstem, hypothalamus, and the cerebellum.These receptors are effectively CO2 receptors,as central [H1] concentrations are directly depen-dent on central PCO2 levels. Central [H1] maydiffer significantly from arterial [H1], as the bloodbrain barrier prevents polar solute diffusion intothe cerebrospinal fluid (CSF). This isolationresults in an indirect central response to mostperipheral acid-base disturbances mediatedthrough changes in partial pressure of arterialcarbon dioxide (PaCO2). Central responses tochanges in PCO2 levels are also slightly delayedfor a few minutes by the location of receptors inthe brain only, rather than in peripheral vasculartissues.Peripheral chemoreceptors include the carotid

bodies and the aortic bodies. The carotid bodies,located bilaterally at the bifurcation of the internaland external carotid arteries, are the primaryperipheral monitors. These highly vascular struc-tures monitor the status of blood about to be deliv-ered to the brain and provide afferent input to themedulla through the ninth cranial nerve. Thecarotid bodies respond mainly to PaO2 but alsoto changes in PaCO2 and pH. Of importance, theydo not respond to lowered oxygen content fromanemia or carbon monoxide (CO) toxicity. Theirmechanisms are integrated, and acute hypoxiainduces an increased sensitivity to changes inPaCO2 and acidosis. Conversely, the response to

low PaO2 is markedly attenuated in the setting oflow PaCO2.Respiratory responses to increases in central

PaCO2 levels above 28 mm Hg are linear withincreases in respiratory rate, tidal volume, andminute ventilation.4 Peripheral PaCO2-drivenresponses also vary with differences in levels ofPaO2. By contrast, the slope of the ventilatoryresponse to PaO2 varies based on sensitivity andthreshold. The response to hypoxia is nonlinearand appears to be minimal above PaO2 levels of60 mm Hg.Resultant interactions of chemoreceptor inputs

regulate normal PaCO2 levels in humans tobetween 37 and 43 mm Hg at sea level. In effect,respiratory control is primarily dependent onPaCO2 with modulation by other factors. Sensitivityof peripheral receptor responses to hypercapniaand hypoxia also increases with a reduction inarterial pH. Whereas acute hypoxia stimulatesincreased sensitivity to PaCO2 peripherally, it mightdepress central respiratory drive.5

Additional feedback to the central controller istransmitted from the lung directly from pulmonarystretch receptors (PSRs) and other afferentpathways. PSRs are located in proximal airwaysmooth muscles, and respond to inflation,especially in the setting of hyperinflation. PSRsmediate a shortened inspiratory and prolongedexpiratory duration. Additional input is alsoprovided by rapidly adapting receptors thatsense flow and irritation. J-receptors are locatedin the juxtacapillary area and appear to mediatedyspnea in the setting of pulmonary vascularcongestion. Bronchial c-fibers also affect bron-chomotor tone and respond to pulmonaryinflammation.Afferent activity from chest-wall and respiratory

muscles additionally influences central controlleractivity. Feedback information regarding musclestretch, loading, and fatigue may affect bothregulatory and somatosensory responses.Upper-airway receptors promote airway patencyby activation of local muscles including the genio-glossus. These receptors may also inhibit thoracicinspiratory muscle activity. Thus, afferent activityenables an appropriate response by centralregulation.The effectors of respiration include the respira-

tory motoneurons and muscles, which areinvolved in inspiration and expiration. Descendingmotoneurons include two anatomically separategroups, the corticospinal tracts and the reticulo-spinal tracts. The phrenic nerve, arising from C3to C5, innervates the diaphragm as the primarymuscle of respiration. Accessory muscles thatassist inspiration include the sternocleidomastoid,

Respiratory Physiology During Sleep 501

intercostal, scalene, and parasternal muscles.These muscles serve to collectively stabilize andexpand the ribcage. Abdominal muscles are activein expiration and may also assist with inspirationduring exercise, or in the setting of chronicobstructive pulmonary disease (COPD) or dia-phragm weakness. Upper-airway muscles activein inspiration include the genioglossus, palatalmuscles, pharyngeal constrictors, and musclesthat pull the hyoid anteriorly. Collectively, thesemuscle groups and motoneurons effect responsesgenerated from central control centers based oninput from multiple receptors. This elegant systemoperates through the complex coordination andinteraction of these subcomponents to continu-ously adapt to changing metabolic needs.

RESPIRATION DURING SLEEP

Regulation of respiration differs significantlybetween sleep and wakefulness. With sleep onset,important changes occur in the various processesthat regulate respiratory control. Behavioral influ-ences on respiration terminate with cessation ofinput from the waking state. Positional changestypically associated with sleep also result in signif-icant alterations in respiratory mechanics. Sleep isa dynamic physiologic state with further varyingeffects on respiration seen in specific sleepstages, particularly in rapid eye movement (REM)in comparison with non–rapid eye movement(NREM) sleep.

Minute ventilation falls with the onset of sleepin response to decreased metabolism and de-creased chemosensitivity to oxygen (O2) andCO2.

6,7 Ventilation during NREM sleep demon-strates an inherently more regular respiratorypattern than wakeful breathing, without significantreductions in mean frequencies. The nadir ofminute ventilation in NREM sleep occurs duringNREM stage 3 (N3) sleep (ie, slow-wave sleep),primarily as a result of reductions in tidal volume.As a result, end-tidal carbon dioxide (ETCO2)during NREM sleep increases by 1 to 2 torrcompared with the waking state.8 During REMsleep, respiratory patterns and control vary moresignificantly. REM sleep respiration is typicallycharacterized by an increased frequency anda reduced regularity. Tidal volume is reducedfurther in comparison with that of NREM sleep, re-sulting in the lowest level of normal minute ventila-tion. Accordingly, ETCO2 increases of an additional1 to 2 torr, often associated with a reduction inoxygen saturation, are seen with the onset ofREM sleep. Metabolic reductions seen in sleepdemonstrate sleep-stage variations with increasedrates in REM compared to NREM sleep.

Ventilatory responses to CO2 and O2 differ insleep in comparison with wakefulness, with impor-tant distinctions between REM and NREM sleep.The linear increases in ventilatory responses toPaCO2 persist during NREM sleep, albeit witha reduced slope compared to wakefulness. Thesechanges appear more evident in males than infemales, who demonstrate reduced CO2

responses while awake with less apparent reduc-tions during NREM sleep.9 In addition, thethreshold of the response to CO2 is shiftedupward, with a higher ETCO2 required to driverespiration in sleep. Responses to increases inETCO2 are further reduced during REM sleep.Respiratory output in sleep, particularly NREMsleep, is significantly reduced in response to hypo-capnia. Respiratory responses to hypoxia appearattenuated during NREM sleep as well, withoutsignificant gender-related differences; hypoxia-induced drive is reduced further in REM sleep.

Of importance, both hypoxia and hypercapniamay trigger arousals from sleep, resulting in a re-turn to the more tightly regulated ventilatorycontrol associated with wakefulness. Arousalthresholds for hypercapnia range between 56and 65 torr, and vary among the different sleepstages. The threshold for arousal in response tohypoxia is more variable and seems less reliable.Severe oxygen desaturations in some individualsdo not uniformly result in arousals.

In addition to the changes in controllerresponses during sleep, the effectors also demon-strate significant sleep-related functional variation.Of the various effectors of respiration, the upper-airway muscles appear to be the most dramati-cally affected by changes occurring with sleep.As described previously, these muscles functionto maintain patency and prevent collapse of theupper airways during inspiration. These musclesprimarily include the genioglossus, tensor palatini,and the sternohyoid, which are active during inspi-ration during wakefulness and are reduced activityduring sleep. The genioglossus responds briskly toincreases in PaCO2 during wakefulness; thisresponse markedly diminishes during sleep.Indeed, the modest increase in PaCO2 seen withsleep onset does not appear to produce a signifi-cant increase in genioglossus activity. Humanstudies of upper-airway responses during REMsleep are limited, with most studies demonstratingthat muscle activity is eliminated by generalizedREM-sleep–associated skeletal muscle atonia;this effect is most prominent during phasic REMsleep. Upper-airway responses to hypoxia gener-ally parallel the responses to hypercapnia. Studiesconsistently demonstrate more striking sleep-related reductions in muscle activity of the upper

Malik et al502

airways than of the diaphragm or accessorymuscles of respiration.Positional changes during sleep (ie, nonupright

position) affect the mechanics of breathing signifi-cantly. Anatomic structures of the upper airwaysmay be more predisposed to collapse, particularlywith the concurrent reductions in upper-airwaymuscle tone. Redundant soft-tissue–related airwaycompromise and retroglossal narrowing of theupper airways may be significantly increased inthe supine position. Subtle increases in vascularcongestion of the airways in response to positionalchanges may also augment airways resistance. Inthe supine position, the contribution of chest-wallexpansion does not exceed the effect of increasedabdominal distention, and functional residualcapacity is thus reduced. Intercostal muscleactivity is significantly increased during NREMsleep compared with wakefulness, and results inproportional increases in the contribution of thechest wall to respiration. With REM-sleep–associ-ated atonia, skeletal muscles associated withrespiration are significantly impaired and ventila-tion is accomplished by the diaphragm alone.Chest-wall compliance is increased with thisdecreased intercostal tone, and paradoxiccollapse of the chest during inspiration may occur.REM sleep is, therefore, associated with relativehypoventilation from both reduced respiratorymechanical capacities and decreased sensitivityof the respiratory drive to hypercapnia andhypoxia.There are significant differences in the responses

to increased airways resistance between sleep andwakefulness. During the waking state, increasedventilatory responses to both elastic loading andairways-resistance loading are present; thisprompt compensation maintains appropriateventilation and prevents development of hyper-capnia. Load compensation is significantlyreduced during sleep. During NREM sleep,moderate levels of elastic loading (18 cm H2O/L)results in decreases in minute ventilation andincreases in ETCO2.

10 Ventilatory effort is thenincreased without normalization back to preloadlevels of ventilation. Lower levels of loading (12cm H2O/L) result in significant ventilatory changesover a few breaths resulting in full compensa-tionwithout arousals.11Waking responses to resis-tance loads include an increase in the duration ofrespiration, an increase in tidal volume, anda decrease in respiratory rate. Minute ventilationis reduced. Responses to increased resistanceduringNREMsleep demonstrate a different patternof reduced tidal volumes and increased respiratoryrates, and no significant change in inspiratory timeratio. Reductions in minute ventilation in response

to resistance loading are more evident duringNREM sleep than in waking states.

MEDICATIONS AND BREATHING DURINGSLEEP

There are several drugs that can impair respirationduring sleep, including alcohol, anesthetics,narcotics, and sedative hypnotics. Conversely,some agents, such as almitrine, acetazolamide,some antidepressants, nicotine, progesterone,theophylline, and thyroid hormones, can stimulatebreathing during sleep.

Drugs that can Impair Respiration

Alcohol, when ingested while awake, can lead toreduction of both hypoxic and hypercapnic venti-latory responses. Irregular breathing with transientapneas can develop. When ingested close tobedtime, it depresses the upper-airway muscletone and may precipitate obstructive sleep apnea,or aggravate a preexisting one; the latter is gener-ally most evident during the first 1 to 3 hours ofsleep when alcohol levels are at their highest.Hypercapnia and significant hypoxemia can occurwith severe intoxication. The risk of sleep-disordered breathing remains elevated in someabstinent alcoholics following long-term habitualalcohol use, possibly caused by residual upper-airway muscle dysfunction or damage to thecentral nervous system.12

Anesthetics can impair the hypoxic ventilatoryresponse, decrease lung volumes, and decreaseupper-airway muscle tone, all of which can leadto significant deterioration of respiratory status inpatients with an existing obstructive sleep apneaor advanced COPD.13

Narcotics are potent respiratory depressantswhich, when ingested at bedtime, can diminishupper-airway muscle tone, give rise to hypox-emia, and decrease the hypercapnic ventilatoryresponse.14

Sedative hypnotics (eg, benzodiazepines orbarbiturates) are mild respiratory depressants.Depression of breathing is be more pronouncedduring coingestion with other central nervoussystem depressants, such as alcohol, or in individ-uals with an underlying respiratory impairment(eg, severe COPD, neuromuscular weakness, orhypoventilation syndromes). Both agents candecrease upper-airwaymuscle activity andworsensleep-disordered breathing; they have variableeffects on central apneas. Whereas they mayincrease the frequency and prolong the durationof hypercapnic forms of central apneas (eg, neuro-muscular disorders), sedative hypnotics may bebeneficial for patients with certain types of

Respiratory Physiology During Sleep 503

nonhypercapnic form of central apnea, such asthose that occur periodically at sleep onset.15

Drugs that can Stimulate Respiration

Almitrine is a respiratory stimulant that enhancesperipheral chemoreceptor sensitivity. Although itcan potentially improve nighttime oxygenation,this effect is generally mild and inconsistent.16,17

Acetazolamide administration induces meta-bolic acidosis from bicarbonate diuresis; this, inturn, can stimulate respiration.18 Although it isbeneficial for the treatment of high-altitude–relatedperiodic breathing, its usefulness for patients withobstructive sleep apnea is limited, inconsistent,and unpredictable.

Certain antidepressants, such as protriptyline,a tricyclic antidepressant, and fluoxetine, a selectiveserotonin reuptake inhibitor, can decrease thefrequency and duration of apneas-hypopneas byincreasingupper-airwaymuscle toneanddecreasingpercentage of REM sleep, during which sleep-disordered breathing tends to be worse than duringNREM sleep.19

Nicotine is a respiratory stimulant. Notwith-standing its effect of enhancing upper-airwaymuscle activity, it has no role in the treatment ofobstructive sleep apnea.20

Progesterone can increase hypoxic and hyper-capnic respiratory responsesaswell asminute venti-lation; it can improve ventilation in patients withobesity-hypoventilation syndrome and decreaseapnea-hypopneas in post-menopausal women.21,22

Theophylline can reverse the bronchospasm ofnocturnal asthma, increase sleep-related oxygensaturation in patients with COPD, and improveCheyne-Stokes crescendo-decrescendo periodicbreathing.23

SLEEP PHYSIOLOGY AND RESPIRATORYDISORDERSNocturnal Asthma

Patients with nocturnal asthma often present withrepetitive arousals and awakenings during thenight accompanied by complaints of breathless-ness, coughing, and wheezing secondary to bron-choconstriction.24 A variety of factors maycontribute to the worsening bronchial reactivitythat occurs during sleep, including a relativeincrease in parasympathetic tone and decreasein nonadrenergic, noncholinergic discharge; com-orbid gastroesophageal reflux or obstructive sleepapnea; circadian changes in levels of endogenoushormones (eg, catecholamines, cortisol, or hista-mine); or reduction of lung volumes and airwaysize. If severe, nocturnal asthma may give rise tosignificant hypoxemia.

Chronic Obstructive Pulmonary Disease

Both hypoxemia and hypercapnia can developduring sleep in patients with COPD. Respiratoryimpairment is more severe during REM sleepthan during NREM sleep. Hypoxemia, the extentof which is related to the percentage of REM sleepin relation to total sleep time as well as daytimelevels of PaCO2, PaO2, and oxygen saturation(SaO2), can result from hypoventilation, ventila-tion/perfusion mismatching, and/or reduction oflung volume (eg, functional residual capacity).COPD can also occur concurrently with obstruc-tive sleep apnea; referred to as the overlapsyndrome; this is associated with worse hypox-emia and greater pulmonary artery pressurescompared with patients with isolated COPD.25,26

Restrictive Lung Disease

Sleep of patients with interstitial lung disease isoften accompanied by frequent arousals. Sleepdisruption appears to be more pronounced inthose with nocturnal oxygen desaturation, theextent of which is influenced by levels of awakePaO2, lung compliance, and age of the patient.27

The increase in respiratory drive that is present inpatients with interstitial lung disease may reducethe prevalence of apneas-hypopneas.

Kyphoscoliosis, by blunting ventilatory drive dueto a greater mechanical load of displacing thethoracic cage, can lead to a number of sleep-related breathing disorders, such as central andobstructive apnea-hypopneas, periodic breathing,hypercapnia and hypoxemia.

Obesity is associated with increased work ofbreathing and greater metabolic demands. Lowerfunctional capacity, less efficient respiratorymuscles, and increased mass loading of thethoracic cage (ie, decrease in compliance) can allgive rise to hypoxemia, which is generally worseduring sleep than during wakefulness because ofthe lower functional residual capacity of a supineposition, relative hypoventilation, and the develop-ment of sleep-related apneas-hypopneas. Ifsevere, obesity can lead to the development ofthe obesity hypoventilation syndrome with itsassociated reductions in hypoxic and hypercapnicventilatory drives.

Pregnancy, like obesity, can reduce lung volumes(eg, functional residual capacity and residualvolume), especially during the third trimester whenweight gain and uterine displacement are maximal.Pregnancymay also be associated with an increasein the prevalence of snoring, owing to structuralchanges and increased compliance of the upperairways. However, apnea-hypopnea frequency andsleep-related hypoxemia tend to be less affected

Malik et al504

because of the augmented ventilatory driveproduced by higher levels of progesterone.

Neuromuscular Disorders

Patients with Duchene muscular dystrophy candevelop hypoventilation and oxygen desaturationduring sleep. Myotonic dystrophy can involve thepharyngolaryngeal and diaphragm muscles;obstructive and central apneas-hypopneas, hypo-ventilation, and oxygen desaturation occurringduring sleep has been described. Poliomyelitis isoften associated with a defective central control ofrespiration and can give rise to apneas andhypopneasduring sleep.Diaphragmparalysis, espe-cially if bilateral, can lead to increases in PaCO2 andreductions in PaO2; these derangements in arterialblood gases are generally worse during REM sleepin comparison with waking and NREM sleep,because of the REM-sleep–related inhibition of theintercostal and accessory respiratory muscles.

Obstructive Sleep Apnea

Upper-airway narrowing and excess weight, ifpresent, can increase the mechanical load on therespiratory system as well as breathing work.Oxygen desaturation can result from repetitiveepisodes of apneas-hypopneas, the latter beingmore common during REM sleep than duringNREM sleep. Episodes of oxygen desaturation,therefore, tend to more frequent and last longerduring REM sleep. Hypoxemia and, to lesserextent, hypercapnia can also arise from the reduc-tion in lung volume related to the supine sleepposition and is made worse by comorbid obesityresulting in augmented respiratory muscle activitygenerated to compensate for the diminished orabsent airflow secondary to upper-airway narrow-ing or collapse (ie, Muller maneuver).

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