Sleep Disordered Breathing

John Conforti, DO SAV Pulmonary Solutions

Pulmonary, Critical Care, Sleep and Interventional Pulmonary Medicine

Washington, Aug 17, (Reuters) Severe sleep apnea raises the risk of dying by 46 percent, U.S., researchers reported on Monday. The risks are most obvious in men aged 40 – 70, Naresh Punjabi of Johns Hopkins University in Baltimore and colleagues found.

Epidemiology

• OSA large individual and public morbidity and mortality • Prevalence study 9.1%M 4%W had an AHI>15 • 24%M and 9%F AHI>5 • 3 million men and 1.5 million women • 12 fold increase in diagnosis 1990-1998 • 1990 ----16B direct and 150B indirect cost

Young T; Palta M; Dempsey J; Skatrud J; Weber S; Badr N Engl J Med 1993 Apr 29;328(17):1230-5.

Normal Sleep Physiology

• Frequency Increases • Tidal Volume Decreases • MV Decreases • PCO2 Increases • PaO2 Decreases

Sleep Definitions

• NREM consists of stages 1 through 4 • REM • Sleep latency • Rem latency • Sleep percentages • Sleep architecture

Architecture

Cardiac Response

• NREM Increases parasympathetic tone • Bradycardia 5-10% • Cardiac Output Decreases • Blood Pressure Decreases • Arrhythmias Of increase vagal tone

Sleep Physiology

• Gastric acid secretion is maximal 10pm and 2am • Swallowing frequency decreases during sleep • Hormonal Association (Leptin, GH) • Thermal regulation is inhibited during REM • Shiver or sweat during NREM

Polysomnography

Rhythms Frequency • Beta ≥ 14 • Alpha 8 to 13 • Theta 4 to 7 • Delta < 4 • Mu 7 to 11 • Spindles 12 to 14

Awake

Grand Rounds Sleep – Stage 1

Prozac causes persistent eye movements

Stage 2

Benzo’s cause hyperspindlemia

Stage 3

Stage 4

REM

Sleep Wake Regulation (All The Neurology You’ll Ever Need To

Know)

Wake • Orexin / Hypocretin • BF – Acetylcholine • VTA – Dopamine • TMB – Histamine • Raphe Nucleus – Serotonin • LC - Norepinephrine

Sleep • VLPA • GABA • Stages 1 / 2 / 3 / 4 • When Loss of Tonic

Inhibition of Pons = REM

Rem Neurotransmitters Pons

PPT / LDT Cholinergic

Hypothalamus

Risk Factors

• Reduced airway size Obesity (central), male

• Craniofacial features Retrognathia, Micrognathia, Macroglossia, etc Modified Mallampati

• Reduce Neuromuscular Output • Gender Differences • Racial Differences

OSA

• Apnea Cessation of breath for 10 seconds • Hypopnea Flow reduction of 50% • AHI Number of events per hour • UARS Upper airway resistance syndrome

• RDI Respiratory disturbance index • RERA Respiratory event related arousals

Clinical Manifestations

• Restless Sleep 100% • Snoring 94% • EDS 78% • Cognitive impairment 58% • Personality changes 48% • Am cephalgia 36% • Nocturia 30% • Insomnia 10%

Epworth Sleepiness Scale

• How likely are you to doze off or fall asleep in the following situations, in contrast to feeling just tired? This refers to your usual way of life in recent times. Even if you have not done some of these things recently try to work out how they would have affected you.

• Use the following scale: • 0=would never doze 1=slight chance of dozing 2=moderate chance of dozing 3=high

chance of dozing

• Situation Score

• Sitting and reading _____ • Watching TV _____ • Sitting inactive in a public place (theatre) _____ • As a passenger in a car for an hour without a break _____ • Lying down in the afternoon when circumstances permit. _____ • Sitting and talking to someone. _____ • Sitting quietly after a lunch without alcohol. _____ • In a car, while stopped for a few minutes in the traffic. _____

The Anatomy Of An Apnea

Outline

• Pharynx • Negative Pressure Airway

Occlusion • Intracardiac Pressures • Pulmonary Artery Pressures • Interventricular Septal

Dependance • LV dysfunction

• Renal Flow • Cerebral Flow • Esophageal Dysfunction • Ischemic Cardiac Disease • Arrhythmia • Systemic Vascular Response

• Genioglossus relaxation • Posterior displacement • Loss of lung volume

• Normal pleural pressures are negative • Occlusion results in large diaphragmatic deflections • NIF / MIP • Pressure generation -100 cm H2O • Measure with transdiaphragmatic pressure gradient

(TDPG) • TDPG and WOB causes arousal

Negative Pressure Pulmonary Edema

• Mueller maneuver • Laryngospasm • Pulmonary edema • Transudation of fluid from the pulmonary capillaries to the

interstitium of the lung • Cytokine mediated • Pleural effusion from negative pleural swings

Willms D; Shure D- Chest 1988 Nov;94(5):1090-2.

Intracardiac Pressures

• Large negative pressure swings • Exaggerates the TDPG • Increases venous return and afterload • RA and RV pressures increase (Preload)

Langanke P. et al. Pneumologie. 1993 Mar;47 Suppl 1:143-6

Pulmonary Artery Pressures

• During the obstruction o Hypoxemia o Hypercapnia PaCO2 = VCO2/VE(1-Vd/Vt) o 2 L TBS of oxygen o 120 L TBS of carbon dioxide o Potent stimulants for Pulmonary vasoconstriction o Pulmonary endothelial remodeling Am J Respir Crit Care Med. 2002 Jan 15;165(2):152-8

PHTN and OSA

• Association is not as firm as SHTN • Respiration. 2001;68(6):562-3 • Am J Respir Crit Care Med. 2002 Jan 15;165(2):152-8 • Arch Intern Med. 2000 Aug 14-28;160(15):2357-62 • 20-40%. Usually mild. Small numbers

Interventricular Septal Dependance

• Increase RV preload • Increase afterload • IVSD • Decrease LV filling chamber size • Decrease cardiac output

Monaldi Arch Chest Dis. 1995 Apr;50(2):129-33

Diastolic Dysfunction

• Increase LV afterload • Decrease LV chamber size • Decrease diastolic relaxation • Transient hypertension • Flash pulmonary edema

Eur Respir J. 2002 Nov;20(5):1239-45

Right Atrial Distention

• Right atrium is the home of atrial natriuretic peptide • Responds to baroreceptor stretch • N=30 • OSA with AHI>15 • Correlated with increase serum and urine ANP

Sleep. 2004 Feb 1;27(1):139-44.

Renal Function

• Elevated ANP • Increase cyclic-GMP • Increase GFR • Increase diuresis • Decrease absorption of Na at ascending limb • Increase incidence of proteinurea • May be HTN related

Neurophysiol Clin. 1989 Jun;19(3):199-207

Map and CBF

• Apnea termination, increase in Map and CBF • Post apnea values of CPP are below baseline • Return to normal within 60 seconds • If repetitive apneas, prolonged reduction

Am J Respir Crit Care Med. 1994 Dec;150(6 Pt 1):1587-91

ICP

• CPP = MAP - ICP • The Ra and RV filling volumes increase • ICP has been shown to increase during apnea • Particularly high during REM • Solely explained by apneas

Chest. 1989 Feb;95(2):279-83

Laryngeal Dysfunction

• GERD from previous mechanisms • GERD worsens OSA • OSA worsens reflux • Chronic GERD

o Laryngospasm o Laryngeal polyps o Dysphagia o Barretts esophagus

Apnea and Heart

• Brady / Tachy • High parasympathetic tone • 10-20% reduction in BP and Pulse • Coronary PP requires a Map and Diastolic Filling • Initial bradycardia is protective

Apnea and Heart

• Middle of Apnea sympathetic outpouring • Tachycardia decreases diastolic filling time • CaO2 drops quickly secondary to hypoxema • Elevated BP post apnea increases afterload, LV

stroke work, Myocardial oxygen demand • Precipitate ischemic events

Evidence

• Eur Heart J. 2004 May;25(9):728-34 n=54 decrease cardiac events

• Am J Respir Crit Care Med. 2000 Jul;162(1):81-6 n=62 untreated was an independent risk factor

• Cardiology. 1999;92(2):79-84 n=263 angiographically proven CAD. 30%

AHI>20 independent risk for MI.

Arrhythmia

• Decrease AV nodal conductivity • High vagal tone during sleep and initial apnea • Decrease Atrial and Ventricular conduction • SA exit block, Atrial ectopic pacer, nodal escape,

ventricular escape, wenckebach block, AV nodal conduction abnormalities

Apnea Termination

• Increase pulse, Increase BP, Decrease SaO2 • SVT • PAT, atrial flutter, atrial fibrillation • VT especially when SaO2 less than 60% • Sudden cardiac death

Systemic Hypertension

• Grote 1999, AJRCCM n=1190 • Lavie 2000, BMJ n=2677 • Nieto 2000, JAMA n=6132

Sleep Heart Health Study (SHHS) • Peppard 2000, N Engl J Med n=709

Wisconsin Cohort Study

Study Review

• Controlled for BMI, smoking, ETOH • Grote controlled for cholesterol, ABG’s • Peppard controlled for neck, waist circumference • Peppard was prospective • Peppard and Lavie used in-lab PSG

Risk Assessment

• Odd ratio ranged from 1.07 to 1.42 for AHI > 1 < 5 • Odds ratio ranged from 1.37 to 2.89 for highest

level of SDB (AHI>15 to AHI > 50) • Each 10 events/hr AHI increases BP by 11%

• Bottom Line: clinically significant (AHI>15) SDB

roughly doubles the risk of hypertension

Results

• The risk of hypertension rises linearly with AHI • Even low levels of SDB increase the risk of

hypertension • Effects of SDB on blood pressure are most

pronounced in under 50

Proposed Ischemic Mechanisms

• Increase sympathetic nerve activity • Endothelin-1 dysregulation • Vascular hypertrophy and impaired relaxation • Elevated CRP

Cheyne Stokes Respiration

Crescendo / Decrescendo breathing • Cardiomyopathy • Independent mortality risk factor • Risk Factors

o Males o Over 60 o Atrial fibrillation o Hypocapnia

• Abnormal loop gain / Circulation time delay • VPAP

OSA

• HTN cause and effect • Lose association PHTN, mild at best. • Car accidents 2 – 7X • Glucose Intolerance • Impotence • EDS • Cognitive impairment

• If AHI > 30 MI / CVA / Vascular Risk / SCD

Diagnostic Studies

• Overnight pulse oximetry • Polysomnography • Sleep laboratory and home studies • Multiple Sleep Latency Test

Severity

• AHI • Normal <5 • Mild >5 ------- <15 • Moderate >15 ----- <30 • Severe >30

Medical Therapy

• Sleep Hygiene • Weight Loss • Dental appliances • Oxygen Therapy - Nasal Canula & Transtracheal • CPAP • BIPAP • REM suppressing medications • Respiratory drive stimulants

WHAT GETS BETTER

• Car accidents • Glucose Tolerance • Subjective, not Objective EDS • Maybe Cognitive function • HTN (By 10 in CPAP / By 5 in OMDS) • IF > 30 prior to treatment, reduction in all cause

cardiovascular events / morbidity / mortality

Which PAP

• CPAP = BiPAP for outcomes and compliance • Auto Titrating CPAP - one study says more

compliance Overall lower airway pressures used P90 used FOT / Airflow resistance As a chronic treatment option As an outpatient titration device No good in centrals and leaks

Improved Compliance

• C-flex is a variable release on exhalation depending on airflow resistance.

• No clear increased compliance • Warm humidification improves compliance • Early follow up and intervention improves

compliance • VPAP for cheynes stokes from cardiomyopathy • Oral Mask Pressures do not correlate with nasal

mask pressures.

Oral Appliances

• Increased compliance over CPAP

• 60-80% • 5 mm reduction in BP • 4 mm underbite • Mild – moderate non-obese

patients • Need teeth • No periodontal disease • No TMJ • Close follow up with

dentistry occlusion difficulties

When Can I drive

• Measurements of driving ability don’t correlate with crashes

• MSLT = No good • MWT = No good • Crash rate .18 - > .06 after one month • Off road events 17.8 - > 9 one month • Marked improvement by 3 days in off road events • Measurable improvement by 2 days decrease

tracking errors • Download CPAP compliance to confirm use

Surgical Treatment

• UPPP • MMHR • UPPP + MMHR • Cochrane data analysis

1) Surgery cannot be recommended routinely • Bariatric surgery cures OSA