SLEEP IN PATIENTS WITH CHRONIC RESPIRATORY DISEASES – A Wake Up Call for Chest Physicians

DR. J.C.SURIMD, DTCD, DNB, FNCCP

Consultant, Professor & HeadDept. of Pulmonary, Critical Care & Sleep

MedicineVardhman Mahavir Medical College &

Safdarjang Hospital, New Delhi

PHYSIOLOGY OF BREATHING

Respiratory center is under the influence of Behavioral inputs from cortical centers via

reticular activating system Chemical inputs from chemoreceptors

responding to PaO2, PaCO2 and pH Mechanoreceptors in the airway, lungs and

chest wall

Phillipson EA Am Rev Respir Dis 1978;118:909-939

Thorsten Schafer. Sleep Apnea. Prog Respir Res. Basel, Karger, 2006, vol 35 pp21-28

THE CENTRAL CONTROL OF BREATHING

Wakefulness (neural)Chemical (Hypoxic & Hypercapnic)Sensory afferent(Mechano receptors)

Motor OutputUpper airwaysDiaphragmIntercostal muscleAccessory muscles

Pattern Generator

Reticular formation

Respective network

RhythmGenerator

Effect of Sleep on Ventilation

Decreased neural output (i.e. drive to breath) Hypotonia of intercostal and accessory muscles

during REM Sleep Shift of ventilatory burden exclusively on the

diaphragm Increased upper airway resistance Decreased responsiveness to hypoxemia and

hypercapnia (i.e. chemosensitivity) Presence of SDB or OHS may further worsen

ventilation

SPECIAL EFFECTS OF REM SLEEP ON ACCESSORY & POSTURAL MUSCLES

REM sleep causes 1. Widespread cortical and medullary neuronal activity 2. Postural & accessory muscle atonia (including upper

airway)3. Intermittent disruption of diaphragm EMG activity.

The ventilatory consequences are 1. Greater dependence on diaphragmatic contraction2. Both VT and f are more variable than in NREM3. A more collapsible upper airway

REM HYPOVENTILATION IN COPD

Fletcher. JAP 1983;54:632-9

SLEEP-DISORDERED BREATHING SECONDARY TO POST-POLIO SYNDROME AND KYPHOSCOLIOSIS

C3/A2

O2/A1

ROC/A1

LOC/A2

Chin EMGRight Anterior Tibialis

Left Anterior Tibialis

ECG

Nasal/oral Airflow

Respiratory Effort – Chest

Respiratory Effort – Abdomen

Oximetry -100%

-- 50%

-- 0%

Stage 2

SaO2 = 88%

Stage 2 Stage 2

Muscle artifact in the LOC and ROC channels

HYPOVENTILATION IN REM SLEEP CAUSED BY LOSS OF ACCESSORY MUSCLE USE IN POST-POLIO PATIENT

C3/A2

O2/A1

ROC/A1

LOC/A2

Chin EMGRight Anterior Tibialis

Left Anterior Tibialis

ECG

Nasal/oral Airflow

Respiratory Effort – Chest

Respiratory Effort – Abdomen

Oximetry

-100%

-- 50%

-- 0%

Stage REM Stage REM Stage 1

SaO2 = 70%

Phasic twitches in leg EMG

Effect of Sleep on Respiratory Muscles

Inspiratory muscles

Awake (Healthy)

Awake (Resp. Disease)

NREM REM

Diaphragm Normal activity High activity Normal activity

Increased

Intercostal Low activity High activity Increased activity

Markedly reduced

Accessory Low activity High activity Normal activity

Markedly reduced

Airway Resistance

Upper airway resistance increases during sleep compared to wakefulness

Marked loss of tonic activity in tongue, pharyngeal, laryngeal and intercostal muscles in REM

Hudgel DW, Martin RJ. J Applied Physiol 1984:56:133-137 Lower airway patency may be compromised .

Nocturnal broncho-contriction seen in 50% asthmatics compared to 8% normal subjects

Hetzel MR, Clark TJH. Thorax 1980;35:732-738

J Appl Physiol 1996;81:282-289

RESISTANCE AND VENTILATION DURING SLEEP

Mouth occlusion pressure (P 0.1) in five adults patients after Added Resistance

Ventilatory compensation to resistive loading occurs during NREM, but whether this compensation is as marked as during wakefulness is not clear

During REM, ventilatory compensation is markedly reduced Wakefulness & NREM before and after addition of

inspiratory resistance of 17 cm H2O/L/s

Iber C J Appl Physiol 1982;52:607-614

Hypoxic Ventilatory Response to Sleep

Douglas NJ Clin Chest Med 1985;6:563

In adult men the hypoxic ventilatory response in NREM sleep is 2/3rd that in wakefulness, falling to 1/3rd of level of wakefulness during REM

In adult women: no change in hypoxic response between wakefulness & NREM but response in REM is ½ that in other stages

Hypercapnic Ventilatory Response

Hypercapnic ventilatory response in adults drops during NREM to about ½ the level in wakefulness and falls further during REM to about 1/3 the level of wakefulness

Gender differences may exist

Douglas NJ Clin Chest Med 1985;6:563

Effect of Sleep Disorders

Obstructive Sleep Apnea Syndrome Sleep related Obesity Hypoventilation

Syndrome Both produce respiratory failure in sleep

Sleep

Cortical

Inputs

Respiratory

Center

sensitivity

Chemoreceptor &

Mechanoreceptor

sensitivity

Respiratory

Muscle

contractility

Lung mechanics:

Airflow resistance

FRC

V/Q relationships

Hypoventilation

Hypoxemia

Hypercapnia

EFFECTS OF SLEEP ON RESPIRATION

CLINICAL SEQUELAE OF HYPOVENTILATION AND DECREASED CHEMOSENSITIVITY

Increase in pCo2 by 2-8 mmHg Decrease in pO2 by 3-10 mmHg or 2% decrease in SaO2 The drop in pO2 , Sao2 and rise in pCO2 is much

more in patients of chronic resp. diseases Disruption of sleep architecture.

Effect of sleep related hypoventilation in health and disease

No significant harmful effect in healthy individuals because of typical shape of the ODC curve.

Significant hypoxia and hypercapnia develops in patients with chronic lung disease. Baseline values of low PO2 and

high PCO2 Significant use of accessory

muscles during wakefulness. Instability of the upper airways

PATHOGENESIS OF DIURNAL RESPIRATORY FAILURESleep

Nocturnal HypoventilationPo2 pCo2

Frequent Arousal

Sleep Disruption

Poor quality of sleep

Sleep deprivation

Decreased Ventilatory Drive to Co2

Bicarbonate retention from the kidney

Normalization of pH

Decreased respiratory drive

Multiple episodes of micro & macro sleep

Daytime Hypersomnolence

Elevated pCo2

Diurnal respiratory failure

Hypoventilation

CONSEQUENCES OF SLEEP RELATED HYPOXEMIA IN PATIENTS WITH RESPIRATORY DISEASES

Symptoms of disrupted sleep Poor sleep Restlessness during sleep Tiredness during awakening, but no

sleepiness Morning headaches

Effect of Nocturnal NIV

Prevents nocturnal hypoventilation Promotes HCO3 secretion from kidneys Normalizes sleep Reduces daytime hypersomnolence Improves chemosensitivity Respiratory muscle rest

SLEEP AND CHRONIC CHRONIC RESPIRATORY DISEASES

COPD ASTHMA NEUROMUSCULAR DISORDERS DPLDs

Sleep and Ventilation in COPD

Loss of enhanced awake central neural drive during sleep

Changes in chemo responsiveness to CO2 is accentuated in COPD patients

Hypoventilation mainly in REM sleep Altered V/Q mismatch Increased upper airway resistance

OXYGEN SATURATION DURING SLEEP IN A PATIENT WITH COPD

Douglas et al. 1979; lancet, I,1-4

Sleep Disordered Breathing and COPD

Co-existing sleep apnoea (overlap syndrome) in severe COPD may very from 10-20%

More than 10% of OSA patients have undiagnosed COPD

Chaouat A, Weitzenbaum E, Kreiger J Am J Respir Crit Care Med 1995; 151:82-86

Bradley TD J Am J Respir Crit care Med 1986; 134:920-924

Predictors of nocturnal desaturation in COPD patients

Nonobese patients with moderate to severe COPD with a H/O progressive decline in ABGs.

Hypercapnic patients with severe chronic bronchitis

Patients who experience oxyHb desaturation during exercise

Nocturnal O2 desaturation is associated with increased likelihood of CRF

INDICATIONS FOR EVALUATION OF SDB IN COPD

Moderate to severe daytime hypoxemia Continued clinical deterioration despite the use of

oxygen therapy Pulmonary and systemic hypertension Heart failure Symptoms suggestive of SDB in patients who

experience worsening hypercapnic failure despite stable spirometry

Diagnostic Approach 

Polysomnography

Oximetry

Portable devices 

Treatment of COPD

Optimize medical management

Oxygen Therapy

Nocturnal NIV plus Oxygen Therapy

Effect of nocturnal NIV on Chronic Stable COPD meta-analysis

Meta-analysis of 4 RCTs

Peter J. Wijkstra. Chest 2003;124;337-343

Effect of nocturnal NIV on Chronic Stable COPD – Multicenter trial

Reduction in hospitalization

Improvement in dyspnea

Better health related quality of life

Reduction in health care cost

Sturani et al Eur Respir J 2002;20:529-38

Short-Term Effect of Controlled Instead of Assisted NIV in COPD

Dellweg et al. RESPIRATORY CARE • DECEMBER 2007 VOL 52 NO 12

Short-Term Effect of Controlled Instead of Assisted NIV in COPD

Dellweg. Et al RESPIRATORY CARE • DECEMBER 2007 VOL 52 NO 12

Short-Term Effect of Controlled Instead of Assisted NIV in COPD

Dellweg et al. RESPIRATORY CARE • DECEMBER 2007 VOL 52 NO 12

Weight Gain in Cachetic COPD Patients Receiving Noninvasive Positive-Pressure Ventilation

Budweiser et al. RESPIRATORY CARE • FEBRUARY 2006 VOL 51 NO 2

Change in body mass index after 6 months and 12 months of noninvasive positive-pressure ventilation, compared to baseline values. * p 0.05. † p 0.01

High-intensity Non-Invasive Positive Pressure Ventilation for stable Hypercapnic COPD

Windisch et al Int. J. Med. Sci. 2009, 6

IPAP (cmH2O) 28.0 ± 5.4 17(min) 42(max) EPAP) (cmH2O) 4.6 ± 1.3 2(min) 9(max)

Conclusions High-intensity NPPV is better tolerated by patients with severe chronic hypercapnic COPD and has been shown to be superior to the conventional and widely-used form of low-intensity NPPV in controlling nocturnal hypoventilation. High-intensity NPPV therefore offers a new promising therapeutic option for these patients. Nocturnal mean6SD arterial carbon dioxide

tension (Paco2) at baseline and at follow-up visits

Dreher et al. Thorax 2010;65:303e308

NIV in pulmonary rehabilitation of COPD patients

Thomas Ko¨hnlein et al. Respiratory Medicine (2009) 103, 1329e1336

Conclusion: nocturnal NIPPV is feasible and enhances the effects of pulmonary rehabilitation in advanced stage COPD.

Effect of NIV on stable COPD (Comparison of Costs)

Enrico M. Clini. Respiration 2009;77:44–50

Impact of sleep on patients with neuromuscular or chest wall disease

Specific diseases

The history of a particular disease may also be helpful in some cases.

Patients with polio who had initial involvement of respiratory, trunk, or bulbar muscles, particularly with associated scoliosis or vocal cord paralysis, are more likely to develop abnormalities of gas exchange during sleep.

Kyphoscoliosis, even in the absence of neuromuscular disease, is associated with nocturnal hypoventilation and obstructive sleep apnea.

Indications for a nighttime sleep study in patients with neuromuscular and chest wall disease

Symptoms of sleep disordered breathing

Arterial blood gases showing hypoventilation (PaCO2 >45 mmHg)

FVC <50 percent predicted Severely reduced Pimax Unexplained cor pulmonale

There are no randomised-controlled trials concerning the outcome of noninvasive ventilation in these conditions, but studies have shown an improved quality of life, physical activity and haemodynamics, normalisation of blood gases and slight improvement in other physiological measures, such as the vital capacity and maximal mouth pressures. Survival in chest wall disorders is 90% at 1 yr and 80% at 5 yrs, and similar figures have been obtained in nonprogressive neuromuscular conditions. If, however, the underlying disorder is deteriorating, particularly if it involves the bulbar muscles, it may limit survival despite the provision of adequate noninvasive ventilatory support.

Shneerson et al. Eur Respir J 2002; 20: 480–487

Kyphoscoliotic Ventilatory Insufficiency Effects of Long-term Nocturnal NIV

Blood Gas Levels and Lung Function Breathing Pattern and Respiratory Muscle Strength*

Cruz Gonzalez. Chest 2003;124;857-862

CONCLUSIONS

Lung diseases can present with a vast array of sleep related breathing abnormalities and symptoms

Sleep induced hypoventilation is the common cause of worsening failure

If night-time symptoms are present or suspected, overnight PSG with the determination of optimal treatment in a laboratory setting are recommended

Treatment of the underlying lung disease is an important first step

Nocturnal NIV can significantly improve daytime symptoms and ABGs