Sonolência excessiva com Polissonografia normal. Geraldo Rizzo

(1)

Sonolência excessiva com

Polissonografia normal

Geraldo Rizzo

www.sonolab.com.br

(2)

Terminologia

• Sonolência normal

: sentida na hora habitual de dormir e

revertida por sono em quantidade adequada

• Sonolência patológica

: propensão aumentada para

adormecer apesar da duração adequada de sono e

ocorrendo em horas impróprias – 0,038% - 0.5%

• Quantidade excessiva de sono (EQS):

9horas, embriaguez

de sono, prejuízo cognitivo, comportamento autonômico,

”brain fog” – 8.9%

• Qualidade deteriorada de vigília (DQW) –

1.6%

• Fadiga normal

: após exercício físico e facilmente revertida

por repouso adequado, ou cansaço real sem aumento da

propensão para o sono; falta de energia.

• Fadiga patológica

: estado auto-reconhecido de exaustão

física ou mental persistente e não aliviada pelo repouso

• Alerta

: capacidade da mente em responder

apropriadamente a estímulos internos e externos

(3)

SONOLÊNCIA EXCESSIVA DIURNA (SED)

• Sonolência excessiva diurna (ICSD-3): incapacidade de

ficar acordado e alerta nos maiores episódios de vigília

do dia, com o sono ocorrendo de forma involuntária ou

em horários inapropriados, quase diariamente, por

pelos menos 3 meses.

(4)

Determinantes da Sonolência

• Homeostático

• Circadiano

• Idade (ontogenia)

• Drogas

• Transtornos do Sono

(5)

Por qualquer causa, gravidade pode ser

influenciada por:

• Postura supina

• Baixo nível de atividade

• Baixo nível de luminosidade

• Refeições copiosas ou com alto teor carboidratos

• Início da tarde (ritmo circadiano)

• Noite de sono ruim

(6)

• SED moderada: 15.2%, acentuada: 4,4% a 6,6 %

• Pelo menos 3 X/semana :5 - 20,6%,

• Associação SED + sono insuficiente:

o

8% população geral (insônia, depressão, SAOS)

o

Prevalência sono insuficiente: 1-4%

Prevalência SED

(7)

J Psychiatr Res. 2012;46(4):422-7.

Determining the level of sleepiness in the

American population and its correlates.

Ohayon MM

Excessive sleepiness is highly prevalent in the

American population. It was strongly

associated with insufficient sleep and various

sleep disorders as well as mental and organic

diseases.

8900 pacientes: sonolência moderada em

19,5% e severa em 11%

(8)

Condições associadas com SED

• Sono insuficiente

(Komada Y et al, 2008)

• Obesidade

(Bixler EO et al, 2005)

• Depressão

(Kjelsberg FN et al, 2005)

• Narcolepsia

(Chokroverty S, 1986)

• Hiperssonias

(Vernet C et al, 2011)

• Síndrome das Pernas Inquietas

(Rodrigues RN et al, 2007)

• PLMS

(Haba-Rubio J et al,2004)

(9)

Condições (CID-10) associadas com

Sonolência Excessiva e PSG Normal

• Hipersonia devido à Medicação ou Substância F11-F19

• Síndrome do Sono Insuficiente F51.12

• Dormidor Longo

• Transtornos do Ritmo Circadiano G47.21-G47.26

• Hipersonia Idiopática G47.11

• Síndrome de Kleine-Levin G47.13

(10)

Hipersonia Idiopática

• A. O paciente tem períodos diários de necessidade irresistível de sono ou

lapsos de sono diurnos ocorrendo por, pelo menos, 3 meses.

• B. Cataplexia não está presente.

• C. MSLT mostra menos de 2 SOREMPs ou nenhum se a latência REM na

PSG prévia foi igual ou menor do que 15 minutos.

• D. Presença de pelo menos um dos seguintes:

–

MSLT mostra uma latência média de sono igual ou inferior a 8 minutos

–

O tempo total de sono nas 24 horas é igual ou maior do que 660 minutos (tipicamente

12-14 horas) numa monitorização polissonográfica de 24 horas ( realizada após correção

da privação crônica de sono), ou por actigrafia + diário de sono (pelo menos 7 dias sem

restrição de sono)

• E. Síndrome do sono insuficiente está descartado

• F. A hipersonolência ou os achados de MSLT não são explicados por

nenhum outro transtorno de sono, doença médica ou psiquiátrica, uso de

drogas ou medicações

(11)

Hipersonia Idiopática

• _{Inércia do sono severa e prolongada (36-66%)}

• _{Sestas longas e não restauradoras (46-78%)}

• _{Eficiência de sono alta na PSG (média 90-94%)}

• _{Sintomas depressivos (20-50%)}

Plante et al, JCSM 2016

• _{Tempo total de sono igual ou maior do que 10}

horas em pelo menos 30% dos pacientes

–

HI com TTS longo (magros e jovens)

–

HI sem TTS longo

(12)

Hipersonia Recorrente ou Síndrome de Kleine-Levin

• A. O paciente apresenta pelo menos 2 episódios recorrentes de sonolência

excessiva e duração de sono, cada um persistindo por 2 dias a 5 semanas

• B. Os episódios recorrem geralmente mais do que 1x por ano e pelo

menos 1x a cada 18 meses.

• C. O paciente apresenta-se alerta e com comportamento, cognição e

humor normais entre os episódios.

• D. O paciente deve apresentar durante os episódios pelo menos um dos

seguintes:

–

Disfunção cognitiva

–

Percepção alterada

–

Distúrbio alimentar (anorexia ou hiperfagia)

–

Comportamento desinibido ( tal como hipersexualidade)

• E. A hipersonolência e sintomas relatados não são melhor explicados por

nenum outro distúrbio de sono, doença médica, neurológica ou

psiquiátrica ou uso de drogas ou medicamentos.

(13)

Hipersonia Recorrente ou Síndrome de Kleine-Levin

• _{SKL relacionado à menstruação (18 casos)}

• _{SKL cerca de 500 casos descritos dos quais 5%}

com história familiar

• _{Aumento da associação com HLA DQB1*02}

• _{EEG sugere encefalopatia multifocal}

• _{Fisiopatologia desconhecida}

(14)

Hipersonia devido à Doença Médica

• A. O paciente tem períodos diários de sono irresistível ou

lapsos diurnos de sono por pelo menos 3 meses.

• B. A sonolência diurna ocorre como consequência de uma

significante condição médica ou neurológica subjacente

• _{C. Se realizado, o MSLT mostra uma latência média de sono}

igual ou inferior a 8 minutos e menos de 2 SOREMPs

• _{D. Os sintomas não são melhor explicados por outro}

transtorno de sono não tratado, doença mental e efeitos de

medicações ou drogas

(15)

Hipersonia devido à Doença Médica

• _{Doenças genéticas associadas com sonolência}

primária do CNS

• _{Hipersonia secundária a infecções, tumores e}

outras lesões do SNC

• _{Hipersonia secundária a Hipotireoidismo}

(16)

• Prevalente

• Co-morbidades médicas, psiquiátricas

• Medicações

• Combinações

• Neuro-degeneração dopaminérgica e

hipocretina

Arnulf I, Leu S, Oudiette D. Abnormal sleep and sleepiness in Parkinson's disease. Curr Opin

Neurol. 2008 Aug;21(4):472-7.

Merello M. Non-motor disorders in Parkinson's disease. Rev Neurol. 2008 Sep

1-15;47(5):261-70. Review.

(17)

• SE: 25% de prevalência no TCE

• Redução Hcrt-1 no LCR

• Perda celular hipocretinas

(18)

Sonolência excessiva diurna em

pacientes com síndrome da apneia

obstrutiva do sono tratada

Geraldo Rizzo

www.sonolab.com.br

(19)

Definição

Sonolência residual em pacientes com apneia

obstrutiva de sono (AOS) corresponde à queixa

subjetiva de sonolência excessiva diurna (SED)

que está presente mesmo quando os parâmetros

de respiração e oxigenação durante o sono estão

normalizados pela terapia específica da AOS. O

instrumento

mais

comumente

usado

para

quantificar a sonolência subjetiva é a Escala de

Sonolência de Epworth ESE)

(20)

Original Article

Obstructive Sleep Apnea Syndrome in the Sao Paulo Epidemiologic Sleep Study

Sergio Tufik

a

_{, Rogerio Santos-Silva}

a

_{, Jose Augusto Taddei}

b

_{, Lia Rita Azeredo Bittencourt}

_a,*

a_{Disciplina de Medicina e Biologia do Sono, Departamento de Psicobiologia, Universidade Federal de Sao Paulo – UNIFESP, Sao Paulo, Brazil} b_{Disciplina de Nutrição e Metabolismo, Departamento de Pediatria, Universidade Federal de Sao Paulo – UNIFESP, Sao Paulo, Brazil}

a r t i c l e

i n f o

Article history: Received 28 July 2009

Received in revised form 24 September 2009

Accepted 2 October 2009 Available online 1 April 2010

Keywords:

Obstructive Sleep Apnea Syndrome Nasal cannula Epidemiology Polysomnography Prevalence Population

a b s t r a c t

Objective: To estimate the prevalence of Obstructive Sleep Apnea Syndrome (OSAS), using current clin-ical and epidemiologclin-ical techniques, among the adult population of Sao Paulo, Brazil.

Methods: This population-based survey used a probabilistic three-stage cluster sample of Sao Paulo inhabitants to represent the population according to gender, age (20–80 years), and socio-economic status. Face-to-face interviews and in-lab full-night polysomnographies using a nasal cannula were performed. The prevalence of OSAS was determined according to the criteria of the most recent Interna-tional Classification of Sleep Disorders (ICDS-2) from American Academy of Sleep Medicine (2005). Results: A total of 1042 volunteers underwent polysomnography (refusal rate = 5.4%). The mean age ± SD was 42 ± 14 years; 55% were women and 60% had a body mass index > 25 kg/m2_{. OSAS was observed in}

32.8% of the participants (95% CI, 29.6–36.3). A multivariate logistic regression model identified several independent and strong associations for the presence of OSAS: men had greater association than women (OR = 4.1; 95% CI, 2.9–5.8; P < 0.001) and obese individuals (OR = 10.5; 95% CI, 7.1–15.7; P < 0.001) than individuals of normal weight. The adjusted association factor increased with age, reaching OR = 34.5 (95% CI, 18.5–64.2; P < 0.001) for 60–80 year olds when compared to the 20–29 year old group. Low socio-eco-nomic status was a protective factor for men (OR = 0.4), but was an associated factor for women (OR = 2.4). Self-reported menopause explained this increased association (age adjusted OR = 2.1; 95% CI, 1.4–3.9; P < 0.001), and it was more frequent in the lowest class (43.1%) than either middle class (26.1%) or upper class (27.8%) women.

Conclusions: This study is the first apnea survey of a large metropolitan area in South America identifying a higher prevalence of OSAS than found in other epidemiological studies. This can be explained by the use of the probabilistic sampling process achieving a very low polysomnography refusal rate, the use of cur-rent techniques and clinical criteria, inclusion of older groups, and the higher prevalence of obesity in the studied population.

1. Introduction

Obstructive Sleep Apnea Syndrome (OSAS) is a significant public health problem associated with hypersomnolence, accidents, car-diovascular morbidity, cognitive impairment, anxiety, depression, and metabolic dysfunction[1–5].

OSAS can be influenced by both genetics and the environment, and it is important to determine the prevalence of OSAS in specific populations. Although OSAS has been studied in North America, Europe, Asia, Australia, and India, no comprehensive studies have been conducted in South America[6–14].

Earlier studies estimated that between 3.7% and 26% of the pop-ulation has an Apnea-Hypopnea Index (AHI) above 5. The

preva-lence of OSAS, defined by AHI frequency and the presence of hypersomnolence, has been estimated to range from 1.2% to 7.5%

[6–14]. These wide variations are partly the result of the lack of homogeneity in epidemiologic studies. Some studies, for example, were performed in pre-selected population groups (e.g., state agency employees, industrial employees, or clinically referred patients) and included a high number of subjects who were suspected of having OSAS because of their snoring frequency

[15]. Moreover, some earlier studies did not include subjects over 60 years of age [6,9–14]. Many studies were conducted before the development of the nasal cannula and used a thermistor to re-cord airflow during sleep, which is a less sensitive device to detect abnormal sleep respiratory events. Finally, earlier investigations did not use the most recent criteria for OSAS diagnosis from the International Classification of Sleep Disorders (ICSD-2, 2005) of the American Academy of Sleep Medicine (AASM)[16]. Previously, significant daytime sleepiness and strictly scored apneas and

*Corresponding author. Address: Rua Napoleao de Barros 925, CEP 04024-002, Sao Paulo/SP, Brazil. Tel.: +55 11 21490155; fax: +55 11 55725092.

E-mail address:[email protected](L.R.A. Bittencourt).

Sleep Medicine 11 (2010) 441–446

Contents lists available atScienceDirect

Sleep Medicine

j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / s l e e p

15 did not have any complaints and were not included in the OSAS

group. If an AHI above 15 had been the only criterion used to

diag-nose OSAS (ICSD-2), only 16.9% of the studied population would

have been identified with OSAS. The frequency of subjects with

OSAS decreased proportionally as other complaints were included.

Table 3

shows that one in three (32.8%) Sao Paulo residents met

the criteria for OSAS. The prevalence estimates are higher among

men and increase in both genders with age. OSAS was also more

prevalent in overweight and obese subjects of both genders. The

higher prevalence of OSAS in women with a low socio-economic

status suggests that gender and socio-economic status may

inter-act. OSAS tends to be more prevalent among people who do not

participate in the work force, and such differences are even greater

when working and non-working women are compared.

In order to quantify the independent participation of each

explanatory variable in the distribution of OSAS, a logistic model

was fitted.

Table 4

shows that gender, age, and BMI were identified

as independent and strong associated factors for the presence of

OSAS. When these variables were controlled, participation in the

work force was not an independent associated factor for OSAS.

To explain the different prevalence trends of OSAS in men and

wo-men of different socio-economic groups, the interaction term was

studied in the multivariate model. Low socio-economic status

was a protective factor for males (OR = 0.4), but was an associated

factor for females (OR = 2.4). After fitting logistic models to explain

the relationship between gender and socio-economic status among

women, the self-report of menopause was identified as an

explan-atory factor for the increased association (age adjusted OR = 2.1;

95% CI, 1.4–3.9; P < 0.001). Self-reported menopause was more

common among low-class women (43.1%) than among

middle-class (26.7%) or upper-middle-class (27.8%) women.

Fig. 1. Frequencies (%) of sleep complaints (loud snoring, daytime sleepiness,

fatigue, and breathing interruptions) considered in the classification of Obstructive

Sleep Apnea Syndrome according to the American Academy of Sleep Medicine

(ICSD-2, 2005), separated by categories of AHI, in a probabilistic sample (n = 1042)

representative of Sao Paulo inhabitants.

Table 3

Weighted prevalence estimates (%) and 95% Confidence Intervals (CI) of Obstructive Sleep Apnea Syndrome by gender, age group, socio-economic status, participation in the work

force, and body mass categories for a probabilistic sample (n = 1042) of Sao Paulo inhabitants.

OSAS

Total

Men

Women

Total

32.9 (29.6–36.3)

40.6 (35.7–45.7)

26.1 (22.5–30.1)

Age groups

20–29y

7.4 (4.9–10.8)

13.4 (8.7–20.0)

1.4 (.7–3.1)

30–39y

24.2 (18.9–30.4)

31.7 (24.1–40.4)

17.6 (10.9–27.1)

40–49y

37.7 (31.9–43.8)

58.9 (49.3–67.7)

18.5 (14.6–23.3)

50–59y

49.2 (40.7–57.7)

55.9 (42.1–68.8)

43.9 (35.9–52.4)

60–69y

60.2 (49.3–70-1)

55.9 (40.7–70.2}

63.4 (48.5–76.2)

70–80y

86.9 (78.4–92-5)

88.7 (77.8–94.7}

85.8 (71.3–93.6)

Socio-economic status

High

35.5 (29.8–41.5)

48.0 (40.9–55.2)

22.4 (16.4–29.8)

Mid

31.5 (28.0–35.1)

38.9 (33.1–45.1)

25.3 (21.9–30.0)

Low

35.6 (24.5–48.6)

26.1 (17.2–37.4)

43.2 (26.4–61.7)

Participation in the work force

Workers

30.1 (27, 33.3)

39.6 (34.9, 44.6)

19.9 (16.1, 24.6)

Non-workers

40.1 (33.8, 47.9)

44.7 (33.2, 56.8)

38.5 (31.1, 46.5)

BMI categories

a

Normal

14.6 (10.9–19.2)

21.2 (14.7–29.5)

8.4 (5.7–12.2)

Overweight

34.5 (30.1–39.1)

41.6 (35.6–47.9)

27.9 (21.8–34.9)

Obese

64.1 (50.4–70.3)

80.8 (71.2–87.8)

52.2 (43.1–61.2)

a

_{Normal = body mass index (BMI) < 25 kg/m2; Overweight = BMI between 25 and 30 kg/m}

2

_{; Obese = BMI > 30 kg/m}

2

_.

Table 4

Multivariate logistic regression final model for Obstructive Sleep Apnea Syndrome in

a probabilistic sample (n = 1042) representative of Sao Paulo inhabitants.

OR (95% CI)

P-value

Gender

Women

1 Men

4.1 (2.9–5.8)

0.00 Age in years

20–29y

1 30–39y

3.9 (2.6–5.8)

0.00 40–49y

6.6 (4.1–10.6)

0.00 50–59y

10.8 (6.9–16.8)

0.00 60–80y

34.5 (18.5–64.2)

0.00 Socio-economic status and women

High and women

1 Mid and women

1.4 (0.7–1.9)

0.61 Low and women

2.4 (1.0–6.3)

0.057 Socio-economic status and men

High and men

1 Mid and men

1.0 (0.6–1.8)

0.00 Low and men

0.4 (0.1–0.9)

0.04 Participation in the work force

Workers

1 Non-workers

0.9 (0.6–1.4)

0.89 BMI category

a

Normal

1 Overweight

2.6 (1.9–3.7)

0.00 Obese

10.5 (7.1–15.7)

0.00

a

_{Normal = body mass index (BMI) < 25 kg/m2; Overweight = BMI between 25}

and 30 kg/m

2

_{; Obese = BMI > 30 kg/m}

2

_.

(21)

•Am J Respir Crit Care Med. 1999;159(2):461-7. Randomized

placebo-controlled crossover trial of continuous positive airway

pressure for mild sleep Apnea/Hypopnea syndrome.

Engleman HM,

Kingshott RN, Wraith PK, Mackay TW, Deary IJ, Douglas NJ.

•Am J Respir Crit Care Med. 2001;164(4):608-13. Effectiveness of

CPAP treatment in daytime function in sleep apnea syndrome: a

randomized controlled study with an optimized placebo.

Montserrat

JM, Ferrer M, Hernandez L, Farré R, Vilagut G, Navajas D, Badia

JR, Carrasco E, De Pablo J, Ballester E.

Arch Intern Med. 2003;163(5):565-71. Continuous positive airway

pressure therapy for treating sleepiness in a diverse population with

obstructive sleep apnea: results of a meta-analysis.

Patel SR, White

DP, Malhotra A, Stanchina ML, Ayas NT.

(22)

Tratamento ideal com

CPAP

• Informar o paciente sobre AOS e suas conseqüências

• Explicar as características principais do aparelho de CPAP:

princípios, controle de pressão, rampa

• Selecionar uma máscara adequada

• O paciente deverá praticar, colocando e tirando a máscara várias

vezes

• O paciente deverá praticar usando o CPAP em vigília por cerca de

1 hora e praticar a mudança de pressão

• Titular o aparelho duante o sono

• Acompanhar o paciente nas primeiras 3 semanas de terapia com

CPAP em casa e depois conforme a necessidade

(23)

Sleep

1996;19(9 Suppl):S117-22. Trends

and somnolence despite initial

treatment of obstructive sleep apnea

syndrome (what to do when an OSAS

patient stays hypersomnolent despite

treatment).

(24)

residual daytime sleepiness was 12%, and when

other sleep disorders and major depression were

excluded as confounders the remaining

preva-lence was 6%.

3

_{However, it is difficult to predict}

the individuals who will have this residual

sleepi-ness because studies have been small and

conflicted.

1,2

When determining the cause of residual

sleepi-ness in CPAP-treated OSA, it should be

remem-bered that, even in community-based samples,

only a very weak association exists between

day-time sleepiness and OSA severity.

4

_Individuals

with mild OSA can have high levels of EDS and

in-dividuals with severe OSA may have no symptoms

of hypersomnolence.

4

_{Factors that may contribute}

to excessive daytime sleepiness (EDS) are shown

in

Fig. 1

and outlined in more detail later.

The accepted prevalence of OSA (defined as an

apnea hypopnea index [AHI] >5) in middle-aged

men is 25% and 15% for women.

5,6

_{More recent}

prevalence estimates are as high as 80% for

men and 60% for women.

7

_{At the same time,}

population-based prevalence estimates of EDS

as measured by the Epworth Sleepiness Scale

(ESS) are around 15%.

4,8,9

_{Even if these conditions}

(OSA and EDS) were completely unrelated, simply

multiplying the prevalence of these two

condi-tions together gives an expected coprevalence of

around 4% to 20%. The accepted prevalence of

sleep apnea syndrome, the combination of OSA

and EDS, is between 4% and 12%

5,6,10

EDS is

also associated with obesity independent of the

effects of OSA.

11

_{It might therefore be that in}

indi-vidual patients only a portion of their daytime

sleep-iness symptoms are attributable to sleep apnea.

The clinical trial data testing CPAP support this,

with mild reductions in daytime sleepiness after

controlling for placebo effects.

12,13

_{EDS may also}

persist in these patients because of long-term

intermittent hypoxia before treatment of OSA,

which may lead to irreversible changes in the brain,

as has been suggested in mouse models.

14

_Studies

examining this patient group have found that they

tend to have more reduced daytime functioning,

fa-tigue, and poorer general health than those without

residual sleepiness.

1,15,16

This article discusses the prevalence and

causes of residual sleepiness in CPAP-treated

OSA, provides a diagnostic work-up for clinicians

encountering this population, and discusses the

treatment of these individuals.

Fatigue or Sleepiness?

Although daytime fatigue and daytime sleepiness

are distinct symptoms, they have overlapping

Fig. 1. Factors in ovals are potential contributing factors to the cause of residual daytime sleepiness in OSA.

Arrows represent the direction of effects.

Chapman et al

2 Downloaded from ClinicalKey.com.au at University of Sydney June 29, 2016.

(25)

• 1047 pacientes: sonolência residual 13%

• Pacientes sem sonolência inicial 5,6%

• Pacientes com sonolência inicial 18,3%

Residual sleepiness in sleep apnea patients treated by

continuous positive airway pressure

M E R C E G A S A1 , 7_{, R E N A U D T A M I S I E R}1 , 2_{, S A N D R I N E H . L A U N O I S}1 , 2_,

M A R C S A P E N E3_{, F R A N C I S M A R T I N}4_{, B R U N O S T A C H}5_{, Y V E S G R I L L E T}6_,

P A T R I C K L E V Y1 , 2 _{and J E A N - L O U I S P E P I N}1 , 2

1_{INSERM U 1042, Joseph Fourier University, HP2 Laboratory (Hypoxia: Pathophysiology), La Tronche, France,}2_{Sleep Laboratory and EFCR,}

Locomotion, Rehabilitation and Physiology Department, Grenoble University Hospital,Grenoble CEDEX 09, France,3_Unit!_{e Sommeil et}

Vigilance, Polyclinique Bordeaux Cauderan, Bordeaux, France, 4

Unit!e des pathologies du sommeil, Centre hospitalier de Compi"egne, Compiegne, France,5_{Service de pneumologie, Clinique Teissier, Valenciennes, France,}6_{Pneumologie, Cabinet priv!}_{e, Valence, France and} 7_{Sleep Unit, Department of Respiratory Medicine, Hospital Universitari de Bellvitge and Bellvitge Biomedical Research Institute (IDIBELL),}

Barcelona, Spain

Keywords

continuous positive airway pressure, depression, residual excessive sleepiness, sleep apnea

Correspondence

Jean Louis P!epin, MD, and Renaud Tamisier, MD, Laboratoire EFCR, CHU de Grenoble, BP217X, 38043 Grenoble cedex 09, France. Tel.: (33+) 4-76-76-55-16;

fax: (33+)-4-76-76-55-86;

e-mails: [email protected] and [email protected]

On behalf of the scientiﬁc council of The Sleep Registry of the French Federation of

Pneumology, (FFP), PARIS, France. Accepted in revised form 9 January 2013; received 20 September 2012

DOI: 10.1111/jsr.12039

SUMMARY

Hypoxic brain damage might explain persistent sleepiness in some continuous positive airway pressure-compliant obstructive sleep apnea called residual excessive sleepiness. Although continuous positive airway pressure may not be fully efﬁcient in treating this symptom, wake-promoting drug prescription in residual excessive sleepiness is no longer allowed by the European Medicines Agency. The aim of this study is to describe residual excessive sleepiness phenotypes in a large prospective sample of patients with obstructive sleep apnea. Residual excessive sleepiness was deﬁned by an Epworth Sleepiness Scale score ! 11. Eligible patients from the French National Sleep Registry attending follow-up continuous positive airway pressure visits numbered 1047. Patients using continuous positive airway pressure < 3 h (n = 275), with residual apnea–hypopnea index > 15 h"1 _{(n = 31) or}

with major depression were excluded (n = 150). Residual excessive sleepiness prevalence in continuous positive airway pressure-treated obstructive sleep apnea was 13% (18% for those with an initial Epworth Sleepiness Scale score > 11), and signiﬁcantly decreased with contin-uous positive airway pressure use (9% in ! 6 h night"1 _continuous

positive airway pressure users, P < 0.005). At the time of diagnosis, patients with residual excessive sleepiness had worse subjective appreciation of their disease (general health scale, Epworth Sleepiness Scale and fatigue score), and complained more frequently of continuous positive airway pressure side-effects. Residual excessive sleepiness prevalence was lower in severe obstructive sleep apnea than in moderate obstructive sleep apnea (11% when AHI > 30 h"1 _versus

18% when AHI 15–30, P < 0.005). There was no relationship between residual excessive sleepiness and body mass index, cardiovascular co-morbidities or diabetes. Continuous positive airway pressure improved symptoms in the whole population, but to a lower extent in patients with residual excessive sleepiness (fatigue scale: "5.2 versus "2.7 in residual excessive sleepiness" and residual excessive sleepiness+ patients, respectively, P < 0.001). Residual excessive sleepiness prev-alence decreased with continuous positive airway pressure compliance. Hypoxic insult is unlikely to explain residual excessive sleepiness as obstructive sleep apnea severity does not seem to be critical. Residual

ª 2013 European Sleep Research Society 389

(26)

Mecanismo da Sonolência Residual

• Hipóxia intermitente e dano cerebral

permanente nas regiões responsáveis pela

regulação do sono e vigília como locus

coeruleus, raphe medial e a região anterior do

cérebro

(Veasey SC et al. 2004 &Zhan G et al. 2005)

• Característica genética e síndrome de

resistência ao CPAP

(Goel N et al.2010)

• Grupo de queixosos

(Vernet et al. 2011)

• Queixa prevalente na população geral

(Ohayon MM

(27)

Residual sleepiness in sleep apnea patients treated by

continuous positive airway pressure

M E R C E G A S A

1 , 7

_{, R E N A U D T A M I S I E R}

1 , 2

_{, S A N D R I N E H . L A U N O I S}

1 , 2

_,

M A R C S A P E N E

3

_{, F R A N C I S M A R T I N}

4

_{, B R U N O S T A C H}

5

_{, Y V E S G R I L L E T}

6

_,

P A T R I C K L E V Y

1 , 2

_{and J E A N - L O U I S P E P I N}

1 , 2

Vigilance, Polyclinique Bordeaux Cauderan, Bordeaux, France,4_Unit!_{e des pathologies du sommeil, Centre hospitalier de Compi"}_egne,

Compiegne, France,5_{Service de pneumologie, Clinique Teissier, Valenciennes, France,}6_{Pneumologie, Cabinet priv!}_{e, Valence, France and} 7_{Sleep Unit, Department of Respiratory Medicine, Hospital Universitari de Bellvitge and Bellvitge Biomedical Research Institute (IDIBELL),}

Barcelona, Spain

Keywords

Correspondence

fax: (33+)-4-76-76-55-86;

DOI: 10.1111/jsr.12039

SUMMARY

Hypoxic brain damage might explain persistent sleepiness in some continuous positive airway pressure-compliant obstructive sleep apnea called residual excessive sleepiness. Although continuous positive airway pressure may not be fully efﬁcient in treating this symptom, wake-promoting drug prescription in residual excessive sleepiness is no longer allowed by the European Medicines Agency. The aim of this study is to describe residual excessive sleepiness phenotypes in a large prospective sample of patients with obstructive sleep apnea. Residual excessive sleepiness was deﬁned by an Epworth Sleepiness Scale score ! 11. Eligible patients from the French National Sleep Registry attending follow-up continuous positive airway pressure visits numbered

1047. Patients using continuous positive airway pressure < 3 h

(n = 275), with residual apnea–hypopnea index > 15 h"1 _{(n = 31) or} with major depression were excluded (n = 150). Residual excessive sleepiness prevalence in continuous positive airway pressure-treated obstructive sleep apnea was 13% (18% for those with an initial Epworth Sleepiness Scale score > 11), and signiﬁcantly decreased with contin-uous positive airway pressure use (9% in ! 6 h night"1 _continuous positive airway pressure users, P < 0.005). At the time of diagnosis, patients with residual excessive sleepiness had worse subjective appreciation of their disease (general health scale, Epworth Sleepiness Scale and fatigue score), and complained more frequently of continuous positive airway pressure side-effects. Residual excessive sleepiness prevalence was lower in severe obstructive sleep apnea than in moderate obstructive sleep apnea (11% when AHI > 30 h"1 _versus 18% when AHI 15–30, P < 0.005). There was no relationship between residual excessive sleepiness and body mass index, cardiovascular

co-morbidities or diabetes. Continuous positive airway pressure

improved symptoms in the whole population, but to a lower extent in patients with residual excessive sleepiness (fatigue scale: "5.2 versus "2.7 in residual excessive sleepiness" and residual excessive sleepiness+ patients, respectively, P < 0.001). Residual excessive sleepiness prev-alence decreased with continuous positive airway pressure compliance. Hypoxic insult is unlikely to explain residual excessive sleepiness as obstructive sleep apnea severity does not seem to be critical. Residual

(28)

• A prevalência da sonolência excessiva residual

diminui com o uso adequado de CPAP.

• Insulto hipóxico não é a explicação mais provável

para a sonolência excessiva residual, uma vez que a

apneia obstrutiva do sono não costuma ser crítica.

• Sintomas residuais não se limitam à sonolência,

sugerindo uma verdadeira síndrome de resistência

ao CPAP e justificando o tratamento com drogas

promotoras da vigília.

Residual sleepiness in sleep apnea patients treated by

continuous positive airway pressure

M E R C E G A S A1 , 7_{, R E N A U D T A M I S I E R}1 , 2_{, S A N D R I N E H . L A U N O I S}1 , 2_,

M A R C S A P E N E3_{, F R A N C I S M A R T I N}4_{, B R U N O S T A C H}5_{, Y V E S G R I L L E T}6_,

P A T R I C K L E V Y1 , 2 _{and J E A N - L O U I S P E P I N}1 , 2

Vigilance, Polyclinique Bordeaux Cauderan, Bordeaux, France, 4

Unit!e des pathologies du sommeil, Centre hospitalier de Compi"egne, Compiegne, France,5_{Service de pneumologie, Clinique Teissier, Valenciennes, France,}6_{Pneumologie, Cabinet priv!}_{e, Valence, France and} 7_{Sleep Unit, Department of Respiratory Medicine, Hospital Universitari de Bellvitge and Bellvitge Biomedical Research Institute (IDIBELL),}

Barcelona, Spain

Keywords

Correspondence

fax: (33+)-4-76-76-55-86;

DOI: 10.1111/jsr.12039

SUMMARY

Hypoxic brain damage might explain persistent sleepiness in some continuous positive airway pressure-compliant obstructive sleep apnea called residual excessive sleepiness. Although continuous positive airway pressure may not be fully efﬁcient in treating this symptom, wake-promoting drug prescription in residual excessive sleepiness is no longer allowed by the European Medicines Agency. The aim of this study is to describe residual excessive sleepiness phenotypes in a large prospective sample of patients with obstructive sleep apnea. Residual excessive sleepiness was deﬁned by an Epworth Sleepiness Scale score ! 11. Eligible patients from the French National Sleep Registry attending follow-up continuous positive airway pressure visits numbered 1047. Patients using continuous positive airway pressure < 3 h (n = 275), with residual apnea–hypopnea index > 15 h"1 _{(n = 31) or}

with major depression were excluded (n = 150). Residual excessive sleepiness prevalence in continuous positive airway pressure-treated obstructive sleep apnea was 13% (18% for those with an initial Epworth Sleepiness Scale score > 11), and signiﬁcantly decreased with contin-uous positive airway pressure use (9% in ! 6 h night"1 _continuous

positive airway pressure users, P < 0.005). At the time of diagnosis, patients with residual excessive sleepiness had worse subjective appreciation of their disease (general health scale, Epworth Sleepiness Scale and fatigue score), and complained more frequently of continuous positive airway pressure side-effects. Residual excessive sleepiness prevalence was lower in severe obstructive sleep apnea than in moderate obstructive sleep apnea (11% when AHI > 30 h"1 _versus

18% when AHI 15–30, P < 0.005). There was no relationship between residual excessive sleepiness and body mass index, cardiovascular co-morbidities or diabetes. Continuous positive airway pressure improved symptoms in the whole population, but to a lower extent in patients with residual excessive sleepiness (fatigue scale: "5.2 versus "2.7 in residual excessive sleepiness" and residual excessive sleepiness+ patients, respectively, P < 0.001). Residual excessive sleepiness prev-alence decreased with continuous positive airway pressure compliance. Hypoxic insult is unlikely to explain residual excessive sleepiness as obstructive sleep apnea severity does not seem to be critical. Residual

(29)

Clínica da Sonolência Residual

• nunca melhorou a sonolência com CPAP

• diagnóstico incorreto de AOS

• tratamento inadequado com CPAP

– Titulação inadequada do CPAP

– Falta de “compliance”

• condições associadas não diagnosticadas: má higiene do sono,

depressão, outros transtornos de sono, ganho secundário

• melhora inicial da sonolência que retornou

depois de algum tempo

• Aumento de peso

• perda da boa adaptação prévia (rinite, nova parceira(o)

• desenvolvimento de novas condições associadas

• perda do efeito “lua-de-mel”/placebo revelando condições

associadas não previamente diagnosticadas.

(30)

Post-CPAP sleepiness – a specific syndrome?

J O H N R . S T R A D L I N G , D E B B I E S M I T H and J O Y C R O S B Y

Oxford Centre for Respiratory Medicine, Churchill Hospital, Oxford, UK

Accepted in revised form 15 August 2007; received 5 July 2007

S U M M A R Y

Following treatment with continuous positive airway pressure (CPAP), some patients

with obstructive sleep apnoea (OSA) remain sleepy despite eﬀective CPAP and

attention to other diagnoses that can provoke sleepiness. It is unclear if this residual

sleepiness is an irreversible result of their previous OSA and merits consideration for

pharmacological treatment or simply because of the many and varied causes of

sleepiness normally found in the community. We have measured levels of sleepiness,

using the Epworth Sleepiness Score (ESS), in 572 patients on CPAP and compared

them with a control group of 525 subjects from a community survey, which would have

included the usual lifestyle reasons for sleepiness as well as any undiagnosed sleep

disorders. There was no diﬀerence in the percentage of patients with an ESS >10 in the

CPAP group compared with the controls (16.1 versus 14.3, P = 0.54). Thus, although

there clearly are sleepy patients within the CPAP group, the prevalence is no higher

than in the community. We question whether so-called

!post-CPAP sleepiness" should

be regarded as any more abnormal and worthy of treatment than a

!normal" population.

Post-CPAP sleepiness as a specific disorder may not exist.

k e y w o r d s

apnoea, continuous positive airway pressure, epworth sleepiness score,

modafinil, sleep apnoea, sleepiness

I N T R O D U C T I O N

Obstructive sleep apnoea (OSA) clearly causes sleepiness,

which responds to continuous positive airway pressure (CPAP)

therapy. However, there is now considerable literature on

continuing sleepiness persisting after CPAP treatment (Black,

2003; Black and Hirshkowitz, 2005; Dinges and Weaver, 2003;

Guilleminault and Philip, 1996; Kingshott et al., 2001; Pack

et al., 2001; Pollak, 2003; Santamaria et al., 2007; Schwartz

et al., 2003). Some papers have shown that much of this

residual sleepiness may be due to inadequate CPAP treatment

(wrong pressures, poor humidification, mask or mouth leaks,

for example) or a second diagnosis, such as periodic limb

movements during sleep (PLMS) (Guilleminault and Philip,

1996; Rodrigues et al., 2007). Despite careful attention to these

possibilities, there still seems to be a small group of patients

with persisting excessive daytime sleepiness, albeit less severe

than before their CPAP treatment (Guilleminault and Philip,

1996). This syndrome of

!post-CPAP sleepiness" is thought

either to be due to permanent brain damage from the OSA in

some way (Santamaria et al., 2007) or to some other aspect of

these patients, such as their obesity (Vgontzas et al., 1998).

However, there are alternative explanations. For example, it

may be that the patients who get suﬃciently sleepy to present

with their OSA in the first place were those already at the

sleepy end of the spectrum before they developed OSA. This

would make it not surprising that, following treatment, they

improve but remain more than averagely sleepy. There is clear

evidence that only some patients with OSA found on a sleep

study are actually symptomatic (Young et al., 1993),

indicat-ing clear inter-individual diﬀerences. Some of these diﬀerences

are likely to be due to variability in susceptibility to sleep

fragmentation (Dinges et al., 1997), but some might simply be

initial tendency to be sleepy. Alternatively it may simply be

that considerable attention is paid to sleepiness in a sleep

clinic, with the Epworth Sleepiness Score (ESS) being filled in

at each follow-up appointment after CPAP. This is likely to

bring it to patients" attention that they might be !abnormal"

when in reality they may be no diﬀerent from a normal

community population.

We recently surveyed a large number of local men and

women for symptoms of sleep apnoea, which included the ESS

Correspondence: J Stradling, Oxford Centre for Respiratory Medicine,

Churchill Hospital, Oxford. OX3 7LJ, UK. Tel.: +44 1865 225 236;

fax: +44 1865 225 221; e-mail: [email protected]

J. Sleep Res. (2007) 16, 436–438

436 ! 2007 European Sleep Research Society

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Síndrome de Resistência ao CPAP

• Sonolência

• Sono não reparador

• Fadiga

• Sintomas depressivos

• Má auto-percepção da saúde

• Pacientes mais jovens e com apneia menos

grave do que os que respondem ao CPAP

(32)

Avaliação da Sonolência Residual

Educational sessions with re-training of the

pa-tients are important to improve the use of CPAP,

particularly in patients with mask claustrophobia in

whom desensitization procedures could be helpful.

It is accepted empirically that compliance is

satisfactory when the patient uses the machine

more than 4.5 h per night. Sleeping with the CPAP

more hours will presumably result in improvements

of sleepiness. Efficacy of therapy should be

assessed at home, using the new devices available,

and only in the cases where compliance is

satisfactory should the diagnostic PSG and titration

procedures be repeated. The next step is to rule

out associated conditions, especially depression

and narcolepsy. Recurrence of sleepiness in a

patient who had initially benefited from CPAP could

be explained by an increase in weight.

3 With

increasing knowledge of sleep disorders in the

general population, there are always those patients

who in order to obtain a pension for chronic

sickness may persist in their complaints of

sleepi-ness or may actually induce it by an insufficient

use of CPAP. Only with a full PSG with CPAP

and an MSLT/MWT on the following day could

these patients be identified. Treatment of

depres-sion may help to improve sleepiness either by

increasing deficient CPAP compliance or by directly

decreasing complaints of sleepiness. Systematic

assessment of depressive symptoms in OSAS

pa-tients is necessary to detect this condition. Given

that sleep clinicians may find it difficult to

differentiate depression and OSAS-related

symp-toms, a brief training program might be useful to

improve their skills in this area. Patients with mild

to moderate depression can be managed by a sleep

physician with antidepressants. Patients with

se-vere depressive symptoms or with no response to an

antidepressant treatment must be referred to a

psychiatrist for assessment.

Finally, when the patient has gone through these

steps and still complains of sleepiness, stimulants

should be prescribed. Modafinil, a wake-promoting

agent used in the treatment of narcolepsy, has

been tested in a number of randomized,

placebo-controlled trials and it has been shown that it

decreases subjective sleepiness and, to some

degree, objective sleepiness

4–6

at 200–400 mg/day.

Practice points

!

Complaints of persistent sleepiness after

CPAP are not uncommon in OSAS patients,

although their prevalence is unknown.

!

There is a protocol to be followed in these

patients that include:

J

Confirmation of the diagnosis of OSAS

and titration procedures (including

as-sessing adequate pressure, mask fit, and

need for humidification; addressing oral

breathing during sleep).

J

Verification of CPAP compliance and

efficacy of therapy at home.

J

Sleep diaries should be filled out by the

patient.

J

Exclusion and treatment of depression

and other sleep disorders (narcolepsy,

poor sleep hygiene, etc.).

J

Possible use of stimulants.

Research agenda

!

Establish the actual prevalence and causes

of persistent sleepiness after CPAP in a large

group of OSAS patients.

ARTICLE IN PRESS

Figure. 3 Suggested procedure to be followed in patients with persistent sleepiness after CPAP.

(33)

J. Santamaria et al. 2007

Lack of compliance

Adequate compliance with CPAP was defined very

freely as using the machine for at least 4 h 5 nights

a week. Compliance rates using these criteria were

around 48–67%.

32,33

However, two concerns should

be raised: (1) clinical improvement could occur

with fewer hours of sleep

34 and (2) the total sleep

time varies among different persons. What could be

enough sleep for one patient may be insufficient for

another, resulting in residual sleepiness. The

percentage of OSAS patients with long-term CPAP

adequate compliance is around 70%

35 a figure that

is comparable to other types of treatment in other

medical disorders.

Improvement in sleepiness with CPAP is not easily

predicted. This does not always depend on the

physiological variables (e.g., AHI, number of

arousals) or CPAP side effects. In a recent study,

upper airway humidification after CPAP did not lead

to better compliance or improvement in sleepiness

or quality of life, although it was associated with

fewer nose symptoms.

36 Fig. 2

shows some reasons

for bad compliance as well as some possible

solutions.

The pattern of nasal CPAP usage is determined

early, usually in the first month

37 and rhinitis is one

of the most important problems. This topic was

reviewed by Engleman and Wild

32 in this journal a

few years ago. Three concepts were highlighted:

(1) relatively expensive high-tech interventions to

improve CPAP use, e.g. ‘‘intelligent’’ CPAP,

humi-dification, are often employed but with relatively

poor results, (2) a multidisciplinary approach and

patient instruction and support are much more

cost-effective, and (3) the cause of bad compliance

should be identified and specific treatment offered.

Our working approach is similar: (1) information

and education sessions before titration (

Table 2

),

(2) careful follow-up especially during the first 4

weeks, and (3) prompt identification and treatment

of the problems. Non compliance with CPAP is

difficult to predict but it could result from a

combination of factors such as lack of clinical

benefits, side effects (rhinitis and leaks) and

inadequate instruction and support.

Undiagnosed associated conditions

Insufficient sleep

A common cause of sleepiness is insufficient

sleep.

38 This is one of the first possibilities to

consider in any patient complaining of sleepiness

and it is also true for the patient with residual

sleepiness after CPAP. Use of sleep diaries or

actigraphic recordings can be of help in assessing

the sleep habits of the patient. It is not easy to

determine what is the minimal amount of sleep

that a particular subject needs to prevent

sleepi-ness but chronic sleep restriction should be

suspected when the patient: (1) has an unusually

high sleep efficiency, (2) reports about 2 h more

ARTICLE IN PRESS

Figure. 2 Suggested clinical procedure to be followed in non compliant CPAP patients. ENT: Ear, nose and throat

specialist.

J. Santamaria et al.

200

(34)