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

                DR. J.C.SURI
            MD, DTCD, DNB, FNCCP
           Consultant, Professor & Head
Dept. of Pulmonary, Critical Care & Sleep Medicine
      Vardhman 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
THE CENTRAL CONTROL OF BREATHING

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


                                        Respective network

                         Rhythm
                         Generator                Pattern
                                                  Generator


                                        Motor Output
                                        Upper airways
                                        Diaphragm
                                        Intercostal muscle
                                        Accessory muscles


Thorsten Schafer. Sleep Apnea. Prog Respir Res. Basel, Karger, 2006, vol 35 pp21-28
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 contraction
   2. Both VT and f are more variable than in NREM
   3. 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                            Muscle artifact in the LOC and ROC channels
                         Stage 2                             Stage 2                          Stage 2
Chin EMG
Right Anterior Tibialis

Left Anterior Tibialis

 ECG


 Nasal/oral Airflow


Respiratory Effort – Chest


Respiratory Effort – Abdomen
          -100%
                                                                                 SaO2 = 88%
Oximetry -- 50%

          -- 0%
                          HYPOVENTILATION IN REM SLEEP CAUSED BY
                          LOSS OF ACCESSORY MUSCLE USE IN POST-
                          POLIO PATIENT

  C3/A2

  O2/A1
 ROC/A1
 LOC/A2
                                                            Stage REM                Stage 1
Chin EMG          Stage REM
Right Anterior Tibialis        Phasic twitches in leg EMG
Left Anterior Tibialis

 ECG


 Nasal/oral Airflow


Respiratory Effort – Chest


Respiratory Effort – Abdomen
                 -100%

Oximetry         -- 50%                                                 SaO2 = 70%
                 -- 0%
              Effect of Sleep on
              Respiratory Muscles

Inspiratory    Awake             Awake           NREM        REM
muscles        (Healthy)         (Resp.
                                 Disease)
Diaphragm      Normal activity   High activity   Normal      Increased
                                                 activity
Intercostal    Low activity      High activity   Increased   Markedly
                                                 activity    reduced
Accessory      Low activity      High activity   Normal      Markedly
                                                 activity    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
RESISTANCE AND VENTILATION DURING SLEEP




                          J Appl Physiol 1996;81:282-289
        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

  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




                                Douglas NJ Clin Chest Med 1985;6:563
          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
                                                       EFFECTS OF
                                                       SLEEP ON
                                Sleep                  RESPIRATION




Cortical Respiratory Chemoreceptor &         Respiratory Lung mechanics:
Inputs   Center        Mechanoreceptor       Muscle      Airflow resistance
         sensitivity   sensitivity           contractility FRC
                                                         V/Q relationships



                           Hypoventilation
                           Hypoxemia
                           Hypercapnia
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 FAILURE
                                   Sleep

                         Nocturnal Hypoventilation
                         Po2 pCo2
                                                         Elevated pCo2
   Frequent Arousal

   Sleep Disruption                                      Bicarbonate retention
                               Daytime                   from the kidney
 Poor quality of sleep         Hypersomnolence
                                                         Normalization of
 Sleep deprivation             Multiple episodes         pH
                               of micro & macro
                               sleep                     Decreased
Decreased Ventilatory
Drive to Co2                                             respiratory drive

                               Hypoventilation


                           Diurnal respiratory failure
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




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

                        Budweiser et al. RESPIRATORY CARE • FEBRUARY 2006 VOL 51 NO 2
          High-intensity Non-Invasive Positive Pressure
          Ventilation for stable Hypercapnic COPD




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

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



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




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

				
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