Diagnosis and Treatment of Obstructive Sleep Apnea in Adults

494 Pages·2011·6.4 MB·English

Comparative Effectiveness Review
Number 32
Diagnosis and
Treatment of
Obstructive Sleep
Apnea in Adults
Comparative Effectiveness Review
Number 32

Diagnosis and Treatment of
Obstructive Sleep Apnea in Adults

Prepared for:
Agency for Healthcare Research and Quality
U.S. Department of Health and Human Services
540 Gaither Road
Rockville, MD 20850
www.ahrq.gov

Contract No. 290-2007-10055-1
14T

Prepared by:
Tufts Evidence-based Practice Center
Tufts Medical Center
Boston, MA

Investigators
Ethan M. Balk, MD, MPH Project Lead, Investigator
Denish Moorthy, MBBS MS, Research Associate
Ndidiamaka O. Obadan, MD MS, Research Associate
Kamal Patel, MPH MBA, Research Associate
Stanley Ip, MD, Investigator
Mei Chung, PhD MPH, Investigator
Raveendhara R. Bannuru, MD, Research Associate
Georgios D. Kitsios, MD, PhD, Research Associate
Srila Sen, MA, Editor
Ramon C. Iovin, PhD, Editor
James M. Gaylor, BA, Research Assistant
Carolyn D’Ambrosio, MD MS, Primary Technical Expert
Joseph Lau, MD, Director, Tufts Evidence-based Practice Center

AHRQ Publication No. 11-EHC052
July 2011
This report is based on research conducted by the Tufts Evidence-based Practice Center (EPC)
under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD
(Contract No. 290-2007-10055-1). The findings and conclusions in this document are those of
the authors, who are responsible for its content, and do not necessarily represent the views of
AHRQ. Therefore, no statement in this report should be construed as an official position of
AHRQ or of the U.S. Department of Health and Human Services.

The information in this report is intended to help health care decisionmakers—patients and
clinicians, health system leaders, and policymakers, among others—make well-informed
decisions and thereby improve the quality of health care services. This report is not intended to
be a substitute for the application of clinical judgment. Anyone who makes decisions concerning
the provision of clinical care should consider this report in the same way as any medical
reference and in conjunction with all other pertinent information, i.e., in the context of available
resources and circumstances presented by individual patients.

This report may be used, in whole or in part, as the basis for development of clinical practice
guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage
policies. AHRQ or U.S. Department of Health and Human Services endorsement of such
derivative products may not be stated or implied.

This document is in the public domain and may be used and reprinted without permission except
those copyrighted materials that are clearly noted in the document. Further reproduction of those
copyrighted materials is prohibited without the specific permission of copyright holders.

None of the investigators has any affiliations or financial involvement that conflicts with the
material presented in this report.

Suggested citation: Balk EM, Moorthy D, Obadan NO, Patel K, Ip S, Chung M, Bannuru RR,
Kitsios GD, Sen S, Iovin RC, Gaylor JM, D’Ambrosio C, Lau J. Diagnosis and Treatment of
Obstructive Sleep Apnea in Adults. Comparative Effectiveness Review No. 32. (Prepared by
Tufts Evidence-based Practice Center under Contract No. 290-2007-10055-1). AHRQ
Publication No. 11-EHC052-EF. Rockville, MD: Agency for Healthcare Research and Quality.
July 2011. Available at: www.effectivehealthcare.ahrq.gov/reports/final.cfm.

ii
Preface
The Agency for Healthcare Research and Quality (AHRQ) conducts the Effective Health
Care Program as part of its mission to organize knowledge and make it available to inform
decisions about health care. As part of the Medicare Prescription Drug, Improvement, and
Modernization Act of 2003, Congress directed AHRQ to conduct and support research on the
comparative outcomes, clinical effectiveness, and appropriateness of pharmaceuticals, devices,
and health care services to meet the needs of Medicare, Medicaid, and the Children’s Health
Insurance Program (CHIP).
AHRQ has an established network of Evidence-based Practice Centers (EPCs) that produce
Evidence Reports/Technology Assessments to assist public- and private-sector organizations in
their efforts to improve the quality of health care. The EPCs now lend their expertise to the
Effective Health Care Program by conducting comparative effectiveness reviews (CERs) of
medications, devices, and other relevant interventions, including strategies for how these items
and services can best be organized, managed, and delivered.
Systematic reviews are the building blocks underlying evidence-based practice; they focus
attention on the strength and limits of evidence from research studies about the effectiveness and
safety of a clinical intervention. In the context of developing recommendations for practice,
systematic reviews are useful because they define the strengths and limits of the evidence,
clarifying whether assertions about the value of the intervention are based on strong evidence
from clinical studies. For more information about systematic reviews, see
http://www.effectivehealthcare.ahrq.gov/reference/purpose.cfm
AHRQ expects that CERs will be helpful to health plans, providers, purchasers, government
programs, and the health care system as a whole. In addition, AHRQ is committed to presenting
information in different formats so that consumers who make decisions about their own and their
family’s health can benefit from the evidence.
Transparency and stakeholder input from are essential to the Effective Health Care Program.
Please visit the Web site (http://www.effectivehealthcare.ahrq.gov) to see draft research
questions and reports or to join an e-mail list to learn about new program products and
opportunities for input. Comparative Effectiveness Reviews will be updated regularly.
We welcome comments on this CER. They may be sent by mail to the Task Order Officer
named below at: Agency for Healthcare Research and Quality, 540 Gaither Road, Rockville, MD
20850, or by e-mail to [email protected].

Carolyn M. Clancy, M.D. Jean Slutsky, P.A., M.S.P.H.
Director Director, Center for Outcomes and Evidence
Agency for Healthcare Research and Quality Agency for Healthcare Research and Quality

Stephanie Chang, M.D., M.P.H. Elisabeth U. Kato, M.D., M.R.P.
Director Task Order Officer
Evidence-based Practice Program Center for Outcomes and Evidence
Center for Outcomes and Evidence Agency for Healthcare Research and Quality
Agency for Healthcare Research and Quality

iii
Technical Expert Panel
Charles Atwood, MD
Director, Sleep Disorders Program
VA Pittsburgh Healthcare System
Pittsburgh, PA

Paul Dallas, MD
Carilion Clinic Internal Medicine
Roanoke, VA

Douglas K. Owens, MD, MS
Director, Stanford-UCSF EPC
Center for Primary Care and Outcomes Research
Stanford University
Palo Alto, CA

Allan Pack, MD, PhD
Professor of Medicine
Director Center for Sleep and Respiratory Neurobiology
University of Pennsylvania

Michael J. Sateia, MD
Director, Sleep Medicine
Dartmouth-Hitchcock Psychiatric Associates
Sleep Disorders Center
Lebanon, NH

Walter Shaffer, MD
Medical Director
Division of Medical Assistance Programs
Salem, OR
Additional Key Informants
Benjamin Chambers
Patient/consumer

Edward Grandi
Executive Director
American Sleep Apnea Assocation
Washington, DC

iv
Leah Hole-Curry, JD
Director, HTA Program
Health Care Authority, State of Washington
Seattle, WA

Amir Qaseem, MD, PhD, MHA, FACP
Senior Medical Associate
Medical Education and Publishing Division
American College of Physicians
Philadelphia, PA

Susan Redline, MD, MPH
Professor of Medicine
Brigham and Women's Hospital
Boston, MA

Paul Shekelle, MD, PhD
RAND Corporation
Director, RAND-Southern California EPC
Santa Monica, CA

John W. Winkelman, MD, PhD
Medical Director
Sleep Health Center
Brigham and Women’s Hospital
Boston, MA

Invited Peer Reviewers
Donna L. Arand, PhD
Clinical Director
Kettering Sleep Disorders Center
Dayton, OH

Douglas C. McCrory, MD, MHS
Scientific Director
Duke Evidence-based Practice Center
Duke Center for Clinical Health Policy Research
Durham, NC

Edmundo R. Rubio, MD
Section Chief, Pulmonary & Critical Care Medicine
Carilion Clinic Sleep Center
Roanoke, VA 24016

v
Michael J. Sateia, MD
Director, Sleep Medicine
Dartmouth-Hitchcock Psychiatric Associates
Sleep Disorders Center
Lebanon, NH

Carl Stepnowski, PhD
Assistant Professor
University of California San Diego
VA San Diego Healthcare System
San Diego, CA

vi
Diagnosis and Treatment of
Obstructive Sleep Apnea in Adults
Structured Abstract
Background. Methods for diagnosing and treating obstructive sleep apnea (OSA) are cumbersome,
resource-intensive, and often inconvenient for the patient.

Purpose. Systematically review the evidence on OSA diagnosis and treatment in adults. The Key
Questions focus on OSA screening and diagnosis, treatments, associations between apnea- hypopnea
index (AHI) and clinical outcomes, and predictors of treatment compliance.

Data Sources. MEDLINE®, Cochrane Central Register of Controlled Trials, and existing systematic
P P
and narrative reviews.

Study selection. Primarily prospective comparative studies of different tests, randomized controlled
trials of treatments, and multivariable association studies. Only published, peer-reviewed, English-
language articles were selected and manually screened based on predetermined eligibility criteria.

Data extraction. A standardized protocol was used to extract details on design, diagnoses,
interventions, outcomes, and quality.

Data synthesis. In total, 234 studies met eligibility criteria (46 on diagnostic tests, 17 predictor studies,
190 on treatments). We found moderate evidence that portable monitors are accurate in diagnosing
OSA (as defined by polysomnography), but retain a variable bias in estimating AHI; low strength of
evidence that the Berlin Questionnaire is able to prescreen patients with OSA with moderate accuracy;
and insufficient evidence to evaluate other questionnaires or clinical prediction rules. No study
adequately addressed phased testing for OSA. There was insufficient evidence on routine preoperative
testing for OSA. High strength of evidence indicates an AHI >30 events/hr is an independent predictor
of death; lesser evidence for other outcomes. We found moderate evidence that continuous positive
airway pressure (CPAP) is an effective treatment for OSA; moderate evidence that autotitrating and
fixed CPAP have similar effects; insufficient evidence regarding comparisons of other CPAP devices;
moderate evidence that oral devices are effective treatment for OSA; moderate evidence that CPAP is
superior to oral devices; and insufficient trial evidence regarding the relative value of most other OSA
interventions, including surgery. We found high and moderate evidence, respectively, that AHI and
Epworth Sleepiness Scale are independent predictors of CPAP compliance, and low evidence that
some treatments improve CPAP compliance.

Limitations. Very few trials evaluated objective clinical outcomes. Data were meager for many
specific questions. Studies were generally of moderate to poor quality, and often had short followups,
high dropout rates, and poor analyses and reporting.

Conclusions. Portable monitors and questionnaires may be effective screening tools, but assessments
with clinical outcomes are necessary to prove their value over polysomnography. CPAP is highly
effective in minimizing AHI and improving sleepiness. Oral devices are also effective, although not as
effective as CPAP. Other interventions, including those to improve compliance, have not been
adequately tested.
vii
Contents
Executive Summary ................................................................................................................ ES-1
12T
Introduction ................................................................................................................................... 1
12T 12T
Diagnosis..................................................................................................................................... 2
12T 12T
Treatment .................................................................................................................................... 5
12T 12T
Statement of Work ...................................................................................................................... 8
12T 12T
Key Questions ............................................................................................................................. 8
12T 12T
Methods ........................................................................................................................................ 10
12T 12T
AHRQ Task Order Officer........................................................................................................ 10
12T 12T
External Expert Input ................................................................................................................ 10
12T 12T
Key Questions ........................................................................................................................... 10
12T 12T
Analytic Framework ................................................................................................................. 11
12T 12T
Literature Search ....................................................................................................................... 11
12T 12T
Study Selection and Eligibility Criteria .................................................................................... 12
12T 12T
Data Extraction and Summaries................................................................................................ 17
12T 12T
Quality Assessment ................................................................................................................... 18
12T 12T
Data Synthesis ........................................................................................................................... 19
12T 12T
Summary Tables ....................................................................................................................... 20
12T 12T
Grading a Body of Evidence for Each Key Question ............................................................... 21
12T 12T
Overall Summary Table ............................................................................................................ 22
12T 12T
Peer Review and Public Commentary ...................................................................................... 23
12T 12T
Results .......................................................................................................................................... 24
12T 12T
Key Question 1 ......................................................................................................................... 25
12T 12T
Comparison of Portable Devices and Polysomnography...................................................... 25
12T 12T
Comparison of Questionnaires and Polysomnography ......................................................... 35
12T 12T
Clinical Prediction Rules and Polysomnography ................................................................. 38
12T 12T
Key Question 2 ......................................................................................................................... 43
12T 12T
Key Question 3 ......................................................................................................................... 44
12T 12T
Key Question 4 ......................................................................................................................... 45
12T 12T
Key Question 5 ......................................................................................................................... 49
12T 12T
Comparison of CPAP and Control ........................................................................................ 50
12T 12T
Comparison of CPAP and Sham CPAP ................................................................................ 58
12T 12T
Comparison of Oral and Nasal CPAP ................................................................................... 66
12T 12T
Comparison of Autotitrating CPAP and Fixed CPAP .......................................................... 67
12T 12T
Comparison of Bilevel CPAP and Fixed CPAP ................................................................... 75
12T 12T
Comparison of Flexible Bilevel CPAP and Fixed CPAP ..................................................... 76
12T 12T
Comparison of C-Flex™ and Fixed CPAP ........................................................................... 77
12T 12T
Comparison of Humidification in CPAP .............................................................................. 78
12T 12T
Comparison of Mandibular Advancement Devices and No Treatment ................................ 80
12T 12T
Comparison of Mandibular Advancement Devices and Inactive (Sham) Oral Devices ...... 87
12T 12T
Comparisons of Different Oral Devices ............................................................................... 89
12T 12T
Comparison of Mandibular Advancement Devices and CPAP ............................................ 91
12T 12T
Comparison of Positional Therapy and CPAP.................................................................... 100
12T 12T
Comparison of Weight Loss Interventions and Control Interventions ............................... 101
12T 12T
Comparison of Oropharyngeal Exercise and Control ......................................................... 103
12T 12T
Comparison of Palatal Implant and Placebo Implant ......................................................... 104
12T 12T
viii
Comparison of Surgery and Control Treatments ................................................................ 105
12T 12T
Comparison of Surgery and CPAP Treatments .................................................................. 107
12T 12T
Comparison of Surgery and Mandibular Advancement Devices ....................................... 110
12T 12T
Comparison of Drug Therapy and Control ......................................................................... 111
12T 12T
Comparison of Atrial Overdrive Pacing and Control or CPAP .......................................... 112
12T 12T
Comparison of Other Interventions and Controls ............................................................... 113
12T 12T
Adverse Events ................................................................................................................... 114
12T 12T
Key Question 6 ....................................................................................................................... 119
12T 12T
Compliance with CPAP ...................................................................................................... 119
12T 12T
Compliance With Mandibular Advancement Devices ....................................................... 121
12T 12T
Key Question 7 ....................................................................................................................... 121
12T 12T
Interventions To Improve Compliance With CPAP Use .................................................... 122
12T 12T
Studies That Evaluated Different Care Models for Patients Who Had CPAP Treatments 124
12T 12T
Summary and Discussion ......................................................................................................... 125
12T 12T
General Discussion ............................................................................................................. 132
12T 12T
Limitations .......................................................................................................................... 137
12T 12T
Future Research ........................................................................................................................ 139
12T 12T
References .................................................................................................................................. 142
12T
Acronyms and Abbreviations ...................................................................................................158
12T
Tables
Table A. Summary of Findings of Studies Addressing Key Questions on Obstructive Sleep
12T
Apnea .................................................................................................................................ES-16
12T
Table 1. Delineation of Operational Rules Used To Classify Monitors in Sleep Studies ...............4
12T 12T
Table 2. Range of Sensitivity and Specificity of Type III Monitors and Type IV Monitors
12T
With ≥3, 2, and 1 Channels ..................................................................................................... 28
12T
Table 3. Descriptions of Clinical Prediction Rules ....................................................................... 42
12T 12T
Table 4. Summary of Findings of Studies Addressing Key Questions on Obstructive Sleep
Apnea .................................................................................................................................... 125
Figures
Figure A. Analytic Framework for the Diagnosis and Treatment of Obstructive Sleep Apnea in
12T
Adults .................................................................................................................................. ES-3
12T
Figure 1. Analytic Framework for the Diagnosis and Treatment of Obstructive Sleep Apnea in
12T
Adults ...................................................................................................................................... 12
12T
Figure 2. Literature Flow .............................................................................................................. 24
12T 12T
Figure 3. Diagnostic Ability of Type III Monitors To Identify AHI Cutoffs Suggestive of
12T
Diagnosis of OSA, and Its Severity, as per Laboratory-Based Polysomnography ................. 29
12T
Figure 4. Diagnostic Ability of Type IV Monitors To Identify AHI Cutoffs Suggestive of
12T
Diagnosis of OSA, and Its Severity, as per Laboratory-Based Polysomnography ................. 34
12T
Figure 5. Diagnostic Ability of the Berlin Questionnaire To Identify AHI Cutoffs Suggestive of
12T
Diagnosis of OSA and Its Severity as per Laboratory-Based Polysomnography ................... 38
12T
Figure 6. Meta-Analysis of AHI (events/hr) in Randomized Controlled Trials of CPAP vs.
Control, by Study Design ........................................................................................................ 54
Figure 7. Meta-Analysis of ESS in Randomized Controlled Trials of CPAP vs. Control, by Study
12T
Design ..................................................................................................................................... 55
12T
ix