Sleep Disorders in ESRD-Why should we care?

Sleep Disorders in ESRD-Why should we care? Dr. Owen Lyons Clinical Research Fellow Division of Respirology, University of Toronto Sleep Research Labo...
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Sleep Disorders in ESRD-Why should we care? Dr. Owen Lyons Clinical Research Fellow Division of Respirology, University of Toronto Sleep Research Laboratory of the UHN-Toronto Rehabilitation Institute

Disclosure • I have no conflict of interests.

Relevance of Sleep in Chronic Kidney Disease • Over 50% of patients with chronic kidney disease complain of sleep quality problems or sleepiness • Sleep disorders very common – Restless Legs Syndrome – Insomnia – Sleep Apnea (Obstructive and Central)

• Implications for quality of life but also morbidity and mortality

Objectives • Sleep

– Why do we need it? – How we measure it

• Sleep Apnea

– What is it? – Why is it important?

• Sleep apnea

– Fluid overload and fluid shift – Epidemiology and clinical features in general population and in patients with chronic kidney disease

• Our current research

– Sleep apnea, hypervolemia and ESRD

SECTION 1 SLEEP

Birds do it, Bees do it.........

Measurements-Polysomnography • • • • • • • •

Airflow Respiratory effort Oxygen saturation & pulse rate End tidal CO2 or transcutaneous CO2 ECG Leg EMG Limb movements Digital Video Body position

International 10-20 system of electrode placement F - frontal lobe C - central lobe P - Parietal lobe T - temporal lobe O – occipital lobe Z – electrodes placed on the midline Left and right hemispheres A1 and A2 on the mastoid process (now labelled M1, M2)

EEG frequencies • Alpha (8-14Hz) normal, waking posterior • Beta (>/ 14Hz) normal, waking anterior •Theta (4-7Hz) normal drowsy, light sleep •Delta ( >4Hz) normal deep sleep

Stage W (wake) Epoch scored as wake if: • >50% is alpha rhythm over the occipital region

Wake: Eyes closed

Sleep Onset

Stage N1 •

In subjects generating α rhythm score stage N1 if α rhythm is attenuated and replaced by low amplitude, mixed frequency activity for >50% of the epoch

Stage N2 •

Stage N2 1. 2.

One or more K complexes not associated with arousals One or more trains of sleep spindles

Stage N2

K Complex

Sleep Spindle

Stage N3 •

Score stage N3 when 20% or more of an epoch consists of slow wave activity:

REM

Polysomnography Summary

SECTION 2 SLEEP APNEA- WHAT IS IT? Effect of UF on sleep apnea severity in ESRD

• “Apnea” – Greek for “without breath” • Obstructive apnea = Blockage of airway during sleep – relaxed throat muscles allow soft tissue to collapse • Temporary suspension of breathing for 10+ seconds

Apnea classification In adults an apnea is classified based on inspiratory effort. 1. Obstructive: associated with continues or increased inspiratory effort throughout the entire period of absent airflow 2. Central: associated with an absence of inspiratory effort throughout the entire period of absent airflow

OSA

Central apnea

Hypopnoea

Severity Apnea-Hypopnea Index (AHI)

What happens after an apnea?

T Douglas Bradley, John S Floras Lancet, Volume 373, Issue 9657, 2009, 82–93

Kaplan–Meier Estimates of the Probability of Event-free Survival among Patients with the Obstructive Sleep Apnea Syndrome and Controls.

OSA syndrome and survival

Yaggi HK et al. N Engl J Med 2005;353:20342041.

Marin et. al. Lancet 2005; 365: 1046–53

Transplant Free Survival: CSR-CSA vs non-CSR-CSA

Transplant-free survival (%)

100 Non-CSR-CSA

80 60

CSR-CSA

40 N = 66 20 0

P=0.032

0

6

12

18

24

30

36

Time (months) Sin D et al. Circulation 2000

42

48

54

60

Prevalence of sleep apnea in comorbidities

Copyright © American College of Chest Physicians. All rights reserved.

From: Sleep Apnea and the KidneySleep Apnea and Chronic Kidney Disease: Is Sleep Apnea a Risk Factor for Chronic Kidney Disease? Chest. 2014;146(4):1114-1122. doi:10.1378/chest.14-0596

Schematic representation of the potential pathways for OSA to cause CKD and specific interventions (uppercase). ACEI = angiotensin-converting enzyme inhibitor; AngII = angiotensin II; Anti-HTN = antihypertensive medication; ARB = angiotensin receptor blocker; Glom..sclerosis = glomerulosclerosis; HIF = hypoxia-inducible factor; HTN = hypertension; Inflamm = inflammation; Pr uria = proteinuria; RAS = renin-angiotensin system; SNS = sympathetic nervous system. See Figure 2 legend for expansion of other abbreviation.

Effect of UF on sleep apnea severity in ESRD

Sleepiness at the wheel OSA –no Rx

Controls

OSA – on CPAP for 3 yrs

Controls 3 yrs later

George CF. Thorax 2001;56:508–512

Treatment with CPAP reduces Motor Vehicle Collisions

Collisions/driver/year

0.50 0.40

OSA

p < 0.001

0.50 0.40

0.30

0.30

0.20

0.20

0.10

0.10

0.00 3 Years Before 3 Years After

0.00

CPAP

Controls

p = ns

3 Years Before 3 Years After

Same Time Frame

George C Thorax 2001; 56:508-512

SECTION 3

SLEEP APNEA – GENERAL POPULATION

Common Signs of Sleep Apnea in General Population • • • • • • • • • • •

Loud or disruptive snoring Gasping or choking during sleep Restless sleep Loss of energy Excessive daytime sleepiness Morning headaches Dry or sore throat Depression, irritability or difficulty concentrating High blood pressure Weight gain ADHD in children/behavioral problems /poor grades

OSA

Risk factors          

Male BMI>30 Neck size 17 or greater Over 40 years of age Family history of OSA Ethnic origin Craniofacial abnormalities  

Small oropharynx Retrognathia/ Micrognathia

  

Instability of respiratory control system Low arousal threshold Fluid overload

Large tongue/ Tonsils/ Uvula/Soft palate Nasal obstruction Other factors?

Maxillo-Mandibular Advancement

UPPP

LAUP

SECTION 4

SLEEP APNEA – CHRONIC KIDNEY DISEASE

Sleep apnea in ESRD -prevalence • Prevalence rates of 50-60% • Sleep Heart Health Study – Hemodialysis patients had higher risk of severe SA – (crude OR 4.07 [95% CI 1.83 to 9.07]) – independent of age, sex, BMI and the presence of cardiovascular diseases.

• High prevalence of central sleep apnea

Date of download: 9/14/2015 Copyright © American College of Chest Physicians. All rights reserved.

From: Sleep Apnea and the KidneySleep Apnea and Chronic Kidney Disease: Is Sleep Apnea a Risk Factor for Chronic Kidney Disease? Chest. 2014;146(4):1114-1122. doi:10.1378/chest.14-0596

Figure Legend: Prevalence of sleep apnea in CKD and ESRD. Patient groups: eGFR ≥ 60 mL/min/1.73 m 2, CKD, and ESRD. The prevalence of sleep apnea increased as eGFR declined (eGFR ≥ 60, 27%; CKD, 41%; ESRD, 57%; P = .002). CSR = Cheyne-Stokes respiration (defined as nasal pressure recording with a characteristic crescendo/decrescendo pattern without airflow limitation); eGFR = estimated glomerular filtration rate; ESRD = end-stage renal disease. See Figure 2 legend for expansion of other abbreviation. (Reprinted with permission from Nicholl et al.39)

Date of download: 9/14/2015 Copyright © American College of Chest Physicians. All rights reserved.

From: Sleep Apnea and the KidneySleep Apnea and Chronic Kidney Disease: Is Sleep Apnea a Risk Factor for Chronic Kidney Disease? Chest. 2014;146(4):1114-1122. doi:10.1378/chest.14-0596

Figure Legend: Prevalence of nocturnal hypoxemia in CKD. Nocturnal hypoxemia was defined as mean arterial oxygen saturation of 20 on baseline study, subjects enrolled and returned 1 week later

Effect of UF on sleep apnea severity in ESRD

Non-dialysis day 1. Ultrafiltration for 4 hours 2. Overnight PSG. Total body and segmental fluid volumes, and upper airway crosssectional area measured preand post- sleep.

Ultrafiltration (UF)  Aimed to remove 2 L of

fluid or 50% of the interdialytic fluid/weight gain over a 4 hour period Urea,HCO3- , venous PCO2 measured pre and post UF

Effect of UF on sleep apnea severity in ESRD

Results

Effect of UF on sleep apnea severity in ESRD

Screened for eligibility (n=80)

Excluded (n=46) -Did not meet inclusion/

exclusion criteria (n=31) -Declined to participate (n=15)

Consented (n=34)

Had baseline study (n=34) AHI ≥ 20 events/hr on baseline sleep study and underwent UF and repeat sleep study (n=19) Analyzed (n=19) Effect of UF on sleep apnea severity in ESRD

Baseline characteristics of subjects Age (years) Male sex, n (%)

53.5 ± 10.4 14 (67)

BMI, kg/m2

23.8 ± 6.9

Neck circumference (cm)

38.4 ± 4.0

LVEF %

62.0 ± 4.0

Hypertension, n (%)

17 (89.5)

Ischemic heart disease, n (%)

1(4.7)

Atrial fibrillation, n (%)

2(10.5)

Diabetes, n (%)

3 (15.8)

OSA:CSA AHI (events/hour)

14:5 43.6 ± 20.4

Ultrafiltration (UF) A mean of 2.1 ± 0.4 litres of fluid was removed by UF. Procedure was well tolerated. Pre- UF

Post-UF

p

Urea, mmol/L

14.3±4.7

13.5±4.8

0.62

HCO3-, mmol/L

25.1±3.1

25.0±3.6

0.83

Venous PCO2, mmHg

42.3±6.1

43.2±7.4

0.42

Effect of UF on sleep apnea severity in ESRD

Effects of UF on weight and fluid

Baseline

Post-UF

p

Body weight , kg

72.4± 14.5 70.0 ± 14.2