SHORT TERM EFFECTS OF NIV ON SLEEP IN END STAGE CF Moran Lavie MD The national center for Cystic Fibrosis Sheba medical center
Sleeping with CF (1) In CF, sleep can place a significant physiologic load on the respiratory system Normal alterations in ventilation and gas exchange with sleep onset can be dramatically exaggerated in advanced lung disease resulting in significant oxygen desaturation and hypercapnia (Francis 1980, Muller 1980, Tepper 1983) Stable CF patients have disrupted sleep that may in part be related to the severity of pulmonary disease (Jankelowitz 2005)
Sleeping with CF (2) Impaired sleep quality, fragmentation & architecture Upper airway obstruction with chronic infection and nasal polyps (Shwachman 1962) Increased work of breathing d/t lower AW obstruction, non optimal muscle position d/t hyperinflation (Dancey 2002) Hypercapnia hypoventilation, decreased reflex drive, muscle fatigue (Skatrud 1983, Fletcher 1983, Hudgel 1983) Blunted sensitivity to carbon dioxide (CO2) (Lwin 1972)
Sleeping with CF (3) Nocturnal Hypoxemia - V/Q mismatching, reduced functional residual capacity (FRC) (Stokes 1980, Muller 1980, Fletcher 1983, Catterall 1985, Braggion 1992) Supine position - worsening hypoxaemia (Stokes 1985) Arousals - often independent of desaturation and not changed with oxygen therapy (Spier 1984) Nocturnal cough (Stokes 1980, Francis 1980) Side effects from medications - beta agonists (Dancey 2002) Anxiety
Sleeping changes in CF Reduced total sleep time and sleep efficiency (Dancey 2002) Increased sleep latency (Dancey 2002) Increased stage 1 sleep (Dancey 2002) decreased REM sleep (Spier 1984) Increased movement arousals and awakenings (n.s) (Dancey 2002) Degree of SDB is related to the severity of the lung disease (Milross 2004)
Sleeping with CF - consequences Repeated nocturnal hypoxia pulmonary hypertension and right ventricular failure poor prognosis (Fraser 1999, Goldring 1964, Stern 1980) Sleep deprivation and fragmentation may depress arousability higher CO2 or lower O2 are required before arousal occurs (Cooper 1982, Bowes 1980, Schiffman 1983)
Cough GE reflux GI problems Pain Medications Other CF Snoring OSAS V/Q inequility Hypoventilation Drive Tonic respiratory Accessory muscle activity Sleep quality Sleep disordered breathing Sleep efficiency WASO Partial sleep restriction Arousals Hypoxia Hypercapnia Oxidative stress Systemic inflammation Alteres immune responses release cytokines Pulmonary hypertension Rt. Ventricular failure Neurodegenerative dysfunction Metabolic risk? Pseudomonas growth?
Treatment with O2 O2 improves saturation during sleep, although often at the expense of a rise in CO2 (Goldring 1964, Moss 1965, Hazinski 1981, Spier 1984, Zinman 1989, Gozal 1997, Milross 2004)
Treatment with NIV NIV is as effective as supplemental oxygen in improving SpO2 during sleep NIV is more effective than oxygen therapy alone in controlling CO2 tension during sleep The improvements in nocturnal oxygenation and reductions in CO2 with NIV were achieved without modification of sleep quality or efficiency (Gozal 1997, Milross 2001, Efrati 2004, Young 2008)
Current study Short term effect of noninvasive ventilation on sleep quality in end stage Cystic Fibrosis patients
Methods Prospective study 8 CF patients End stage lung disease (FEV1 < 40%) Sleep study ½ night w/o BIPAP (w/w.o O2) ½ night w BIPAP (n=5) w/o BIPAP data compared to w BIPAP data Each patient compared to himself (n=5)
Demographics Age Mutations Fev1 BMI Patient 1 T.I Patient 2 Z.Y Patient 3 A.O Patient 4 A.Y Patient 5 B.B Patient 6 M.G Patient 7 P.O Patient 8 C.O 30 DF508/DF508 30-45% 19.3 32 DF508/W1282X 26-29% 18.1 17 DF508/405 23-40% 17 23 DF508/405 21-29% 16 23 DF508/VAL470met 23-35% 20.7 34 DF508/DF508 24-44% 23 35 W1282X/W1282X 22-26% 17.4 25 DF508/DF508 21-30% 21.6
Sleep in end-stage patients using BIPAP vs. patients w/o Trend toward Longer sleep latency More SWS %TST Lower arousals Index (per hr)
Trend toward longer sleep latency
Trend toward more SWS %TST
Trend toward lower arousals Index (per hr)
Split night study with and w/o BIPAP (n=5) Lower respiratory rate (P< 0.05) Less time with saturation < 90% (P< 0.05) Trend toward Lower pulse
Lower respiratory rate 27+2 vs. 23+3, p=0.0046
Less time saturation <90%
Trend toward lower pulse
Conclusions sleeping with NIV Lower respiratory rate Less time with saturation < 90% Trend toward lower pulse At the cost of longer sleep latency
Discussion (1) Increased RR Decreased tidal volume Higher energy consumption Muscle fatigue Higher cardiac requirements Reversed with BiPAP
Discussion (2) Decrease in respiratory rate unloading of inspiratory muscles with a possible reduction in the oxygen cost of breathing BIPAP increase in tidal volume and prevention of airway closure with maintenance of endexpiratory lung volume Improvement in oxygenation
Limitations Small study Short term outcome Matching difficulty Goal recruit more patients
Contribution Dr. Amir Szeinberg Dr. Daphna Vilozni Ms. Irina Shapira Dr. Ifat Sarouk Dr. Bat El Bar Aluma Dr. Adi Dagan Dr. Moshe Ashkenazi Dr. Yael Bezalel Prof Ori Efrati
Thank you!