Recognition and Management of High Loop Gain Sleep Apnea

Transcription

1 Recognition and Management of High Loop Gain Sleep Apnea Robert Joseph Thomas, M.D. Beth Israel Deaconess Medical Center, Boston, MA Associate Professor of Medicine, Harvard Medical School NEPS 2016

2 Conflicts and support MyCardio LLC: ECG-spectrogram patent, license Patent: CO 2 device for central / complex apnea DeVilbiss-Drive: Grant, intellectual property, past consulting NHLBI Periodic breathing foundation & Robert Daly

3 Why do we not do better? Sleep apnea phenotypes Pathophysiological phenotypes Obstruction Airway collapsibility, genioglossus responsiveness Arousal threshold Loop gain Central (hypocapnic usually, but not always) Hypoventilation Sleep fragmentation Sleep regulatory phenotypes Long and short sleep Downstream phenotypes Recovery phenotypes

4 Downstream phenotypes Subjective sleepiness Fatigue Pain sensitization Cognitive impairment Dysexecutive syndrome Affective disorder Inflammation Metabolic Endothelial-vascular Cardiac Chemoreflex sensitization Hypertension

5 Recovery phenotypes (time Immediate scales) Sleep quality, rebound stages and states, subjective sleepiness Intermediate (weeks to few months) Hypertension, metabolic, cognition, brain functional and structural networks, chemoreflex sensitization, upper airway neuropathy, migraine Delayed (months to years) Cardiac-vascular remodeling, brain networks, endothelial function Permanent (never return to normal?) Brain structural network, atherosclerosis, cognition

6 A minimum approach to SDB Adaptive Ventilation Control Oxygen Carbon dioxide Drugs: T, Ac, others Obstruction Hypoventilation Minimize iatrogenic Mechanics The target is to understand and then change system behavior Minimize SW transitions Induce stable NREM sleep Sleep

7

8 The phenotype problem

9

10 Strong chemoreflex influences are underestimated Scoring is biased to obstruction Periodic breathing not usually scored ICSD-2 explicitly considers mixed apnea as obstructive Central hypopnea is not usually scored Desaturation linked criteria underestimates Flow limitation is considered a marker of primary obstruction (ICSD-2) CAI threshold of 5 is too high, and requiring 50% of events being central is even worse These are convenience / insurance coverage rather than biologically based

11 ICSD-3 Improvements and new problems Various CSA categories Treatment-emergent CSA is one of them Accepts co-existences High bar (> ) 50 % of events should be central In principle, central hypopneas need to be scored but is optional and no one does it, so. CAHI becomes CAI Using a CAI threshold of 5 and 50% of events misses most of chemoreflex activation Central hypopnea rules in manual are wrong

12 The phenotype of sleep state Wake-NREM-REM NREM is bimodal

13

14

15 Detection of Chemoreflex (high loop gain) Phenotype Assessment during stable NREM sleep NREM CO 2 reserve (Dempsey method) Proportional assist ventilation (Younes method) Dial down (Wellman method) Assessment during unstable NREM sleep Conventional central apnea / periodic breathing scoring (arbitrary, biased) NREM vs. REM dominance (too blurred) Visual inspection and description (subjective) Oscillatory mapping Single signal: oximetry, HRV, flow Coupled

16 CO 2 reserve Dempsey method

17 Chemoreflex strength - Wellman

18 Proportional Assist Ventilation - Younes

19 Wellman s group-from standard PSG MATLAB program, needs arousal scoring and flow measures. NREM dominance and short cycles also consistent with high loop gain. European Respiratory Journal 2015; 45:

20 Phenotyping risk

21 Baseline Study Baseline AHI 5.16, RDI 40.07, Oxygen saturation nadir 88%.

22 Attempt at CPAP

23 Attempt at CPAP: 5 minute view

24

25

26

27 Home sleep study

28 Home sleep study

29 Home sleep study

30 Opiate dysintegrative pattern

31 The phenotype of therapeutic failure CPAP Adaptive ventilators

32

33

34

35

36 Adaptive Ventilation Different machines (available and in development) ResMed Adapt SV, Respironics BiPAP SV Auto Advanced Very different machines, complex internal algorithms Pressure profiles are different Tries to keep ventilation a target % of averaged shortterm means Both can improve AND destabilize breathing Respiratory pro-arrhythmia Power machines that need to be used with skill and care

37 Pressure cycling can come..

38 Pressure cycling can go.

39 Persistent pressure cycling can persist

40 AirCurve 10 ASV pressure cycling

41 ASV pressure cycling

42 ASV-uncompressed

43 #1 CPAP, NV, acetazolamide, zolpidem

44 #1 ASV, acetazolamide, NV, zolpidem

45 #1 Adapt SV, acetazolamide, NV, zolpidem

46 #2 ASV

47 #2Transition to CPAP

48 #2 Transition to stable breathing

49 BiPAP AutoSV Advanced, O2, NV, acetazolamide, temazepam

50 Auto SV - decompressing

51 Auto SV - decompressed

52 AutoSV Advanced note pressure cycling

53 Bench Testing of ASV s Unable to create stable breathing Devices respond but do not enable system stability Zhu K, Kharboutly H, Ma J, Bouzit M, Escourrou P. Bench test evaluation of adaptive servoventilation devices for sleep apnea treatment. J Clin Sleep Med 2013;9:

54 What can we do about failure Recognize Target pathophysiology Track Repeat

55 We Have Four More Options For Use With PAP 1. Give oxygen prevent hypoxia 2. Give sedating drugs stabilize sleep 3. Give small doses of inhaled CO 2 4. Acetazolamide decrease loop gain, increase delta CO 2 Using all or some of these will permit PAP to work

56 NREM sleep, pre-papgam BiPAP 12/8 + 4L / minute O2

57 NREM sleep, PAPGAM BiPAP 12/ % CO2, no O2

58 Low concentration CO 2 effects

59 Enhanced Expiratory Rebreathing Space (Dead space) Published reports: central sleep apnea, congestive heart failure Problem: cc, lack of PAP benefits in CHF, no upper airway support, partial effectiveness Dead space adjunct to PAP patients with complex disease (100+ CHF) -non-vented oronasal mask ml additional EERS

60

61

62

63 Unstable breathing in CHF

64 50 EERs added

65

66 Oxygen Long history of use for central sleep apnea, with or without congestive heart failure Clinically used off-label Intermittent reports Improves but leave behind residual disease Can be combined with PAP More likely effective in high loop gain patients Can help even if saturations already in 90 s Insurance coverage may not be possible if patients do not desaturate to lung levels As a group, hypocapnic central sleep apnea patients hyperventilate so, hypoxia in the conventional sense is less common

67 CPAP refractory

68 CPAP refractory, now with EERS

69 CPAP refractory, now with EERS + 4 L O2

70 Provent for central sleep apnea / periodic breathing

71 Provent for central sleep apnea / periodic breathing

72 Acetazolamide Carbonic anhydrase inhibitor (original idea) Direct reduction of CB activity, effects on aquaporin channels, redox (new thinking) Reports in mixed and central sleep apnea / CSR (including congestive heart failure) Residual disease is universal Greatest effect in those with high loop gain High altitude effectiveness and CPAP users exposed to altitude Temazepam vs. acetazolamide, subjective sleep effects better with benzodiazepine

73 Acetazolamide + CPAP in complex apnea

74 Use of sedatives Normally considered verboten! Sedatives can kill!! Lack of proper phenotyping is the core cause of this misconception Sedatives are appropriate for NREM-dominant sleep apnea (aka altitude-like) Data from several reports - sedatives benefit breathing at altitude (classic and non classic benzodiazepines) Those with low arousal threshold likely benefit most (Eckert DJ, et al Clin Sci 2011;120:

75 How do I use sedatives NREM-dominant apnea / periodic breathing Recognize the sleep fragmentation phenotype some combination of N1 > 30%, efficiency < 70% (70-80 borderline) Prolonged sleep-wake transitions Slow return to sleep (full micro-wake after arousal or slow waves only > 5 seconds after arousal) No / minimal non-cap (N3 per se too scarce to use) Poor clinical tolerance despite reasonable lab efficacy in complex apnea patients Approaches to use Bedtime: zolpidem 5 /10 (women/men) mg or clonazepam 0.5 mg Pharmacological challenge: during study, zolpidem or zaleplon

76 What about hypoventilation No CO 2 monitoring = too bad, tough, you will never know

77 Hypercapnic periodic breathing Periodic breathing is supposed to be hypocapnic Hypoventilation is by definition hypercapnic There cannot be hypocapnic hypoventilation Can there be hypercapnic periodic breathing? Subset of patients Obesity, usually morbid, or COPD + CHF CO 2 is in 50 s or 60 s Breathing pattern is SHORT cycle periodic Acetazolamide helps

78

79 Summary Recognize NREM dominance Self-similar events Pressure cycling Manage Reduce loop gain Stabilize sleep Ignore AASM rules

80 Thank you for the ear Welcome to MD nights at BIDMC-Needham, Fridays, about 15 times a year ( the worst of the worst )