Hyperbaric Oxygen Therapy for Brain Injury - AHRQ Archive

287 Pages·2005·1.19 MB·English

Evidence Report/Technology Assessment
Number 85
Hyperbaric Oxygen Therapy for Brain Injury, Cerebral
Palsy, and Stroke

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. 290-97-0018

Prepared by:
Oregon Health & Science University Evidence-based Practice Center
Portland, Oregon

Marian S. McDonagh, PharmD, Principal Investigator
Susan Carson, MPH
Joan S. Ash, MLS, MBA, PhD
Barry S. Russman, MD
P. Zoë Stavri, PhD
Kathryn Pyle Krages, AMLS, MA
Mark Helfand, MD, MS, EPC Director

AHRQ Publication No. 03-E050
September 2003
This document is in the public domain and may be used and reprinted without permission except
those copyrighted materials noted for which further reproduction is prohibited without the
specific permission of copyright holders.

Suggested Citation:
McDonagh M, Carson S, Ash J, et al. Hyperbaric Oxygen Therapy for Brain Injury, Cerebral
Palsy, and Stroke. Evidence Report/Technology Assessment No. 85 (Prepared by the Oregon
Health & Science University Evidence-based Practice Center under Contract No 290-97-0018).
AHRQ Publication No. 03-E050. Rockville, MD: Agency for Healthcare Research and Quality.
September 2003.

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 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.

AHRQ is the lead Federal agency charged with supporting research designed to improve the
quality of health care, reduce its cost, address patient safety and medical errors, and broaden
access to essential services. AHRQ sponsors and conducts research that provides evidence-
based information on health care outcomes; quality; and cost, use, and access. The
information helps health care decisionmakers—patients and clinicians, health system leaders,
and policymakers—make more informed decisions and improve the quality of health care
services.
ii
Preface

The Agency for Healthcare Research and Quality (AHRQ), through its Evidence-Based
Practice Centers (EPCs), sponsors the development of evidence reports and technology
assessments to assist public- and private-sector organizations in their efforts to improve the
quality of health care in the United States. The reports and assessments provide organizations
with comprehensive, science-based information on common, costly medical conditions and new
health care technologies. The EPCs systematically review the relevant scientific literature on
topics assigned to them by AHRQ and conduct additional analyses when appropriate prior to
developing their reports and assessments.
To bring the broadest range of experts into the development of evidence reports and health
technology assessments, AHRQ encourages the EPCs to form partnerships and enter into
collaborations with other medical and research organizations. The EPCs work with these partner
organizations to ensure that the evidence reports and technology assessments they produce will
become building blocks for health care quality improvement projects throughout the Nation. The
reports undergo peer review prior to their release.
AHRQ expects that the EPC evidence reports and technology assessments will inform
individual health plans, providers, and purchasers as well as the health care system as a whole by
providing important information to help improve health care quality.
We welcome written comments on this evidence report. They may be sent to: Director,
Center for Practice and Technology Assessment, Agency for Healthcare Research and Quality,
540 Gaither Road, Rockville, MD 20850.

Carolyn Clancy, M.D. Jean Slutsky, P.A., M.S.P.H.
Director Acting Director, Center for Practice and
Agency for Healthcare Research and Quality Technology Assessment
Agency for Healthcare Research and Quality

The authors of this report are responsible for its content. Statements in the report should not be
construed as endorsement by the Agency for Healthcare Research and Quality or the U.S.
Department of Health and Human Services of a particular drug, device, test, treatment, or other
clinical service.

ii i
Acknowledgments

The research team would like to express our regard and appreciation for the efforts of Martha
Swain for editing, Daphne Plaut, MLS, for information services, Debra Burch and Carole Reule
for secretarial support, Susan Wingenfeld for program support, and Rosaly Correa-de-Araujo,
MD, MSc, PhD, of the Agency for Healthcare Research and Quality for advice as our Task
Order Officer.
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Structured Abstract

Objectives. The purpose of this report is to describe the methods, results, and conclusions of
a literature review of the benefits and harms of hyperbaric oxygen therapy (HBOT) for brain
injury, cerebral palsy, and stroke.

Search Strategy. We searched MEDLINE, PreMEDLINE, EMBASE, CINAHL, the
Cochrane Library, the Health Technology Assessment Database, HealthSTAR, AltHealthWatch
and MANTIS from inception to March 2001, using terms for hyperbaric oxygen therapy, brain
injury, cerebral palsy, and stroke. We also searched additional databases recommended by
experts, meeting abstracts, conference proceedings, and reference lists. Peer reviewers and
reference lists of included studies were queried for additional studies. The search was updated in
February 2002, and July 2003.

Selection Criteria. Two reviewers independently assessed each title and abstract using
predetermined inclusion criteria based on intervention, population, outcome measures, and study
design criteria. Full papers, reports, and meeting abstracts that met inclusion criteria were
retrieved and reviewed independently by two reviewers.

Data Collection and Analysis. Extraction of data from studies was performed by one
reviewer and checked by a second reviewer. Each study was assessed for quality using
predetermined criteria. An overall assessment of each body of literature was made based on the
internal and external validity, and consistency and coherence of the results of studies.

Main Results. For traumatic brain injury, the evidence about effectiveness is conflicting.
One trial found a significant decrease in mortality, associated with an increase in severe
disability among those who survived. The other found no difference overall, but a significant
reduction in mortality in one subgroup. Together, these studies provided insufficient evidence to
determine whether the benefits of HBOT outweigh the potential harms. For other types of brain
injury, no good- or fair-quality studies were found. For cerebral palsy, the results of the only
truly randomized trial were difficult to interpret because of the use of pressurized room air in the
control group. Patients who received HBOT and those who received pressurized air improved to
a similar degree. No controlled trial of HBOT was designed to measure mortality in stroke
patients, and the best studies found no improvement in neurological outcomes. Evidence about
the type, frequency, and severity of adverse events in actual practice is inadequate. Reporting of
adverse effects was limited, and no study was designed specifically to assess adverse effects.

Conclusions. Evidence from well-conducted clinical studies is limited. The balance of benefits
and harms of HBOT for brain injury, cerebral palsy, or stroke has not been adequately studied.
Future research of HBOT should include dose-ranging and safety studies to establish the
optimum course of HBOT to evaluate in outcome studies. Future clinical trials should include
several treatment options and should evaluate measure caregiver burden in addition to patients’
functional outcomes.

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Contents

Summary ............................................................................................................................. 1

EVIDENCE REPORT

Chapter 1. Introduction ........................................................................................................ 13
Purpose .................................................................................................................... 13
Background ............................................................................................................. 14
Traumatic Brain Injury ................................................................................ 14
Anoxic-ischemic Brain Injury ..................................................................... 17
Cerebral Palsy ............................................................................................. 17
Stroke .......................................................................................................... 18
Hyperbaric Oxygen Therapy ....................................................................... 18

Chapter 2. Methododology .................................................................................................. 25
Technical Expert Advisory Group ........................................................................... 25
Scope and Key Questions ......................................................................................... 25
Intervention .................................................................................................. 25
Population .................................................................................................... 26
Outcomes ..................................................................................................... 26
Design .......................................................................................................... 26
Literature Search Strategy ....................................................................................... 26
Electronic Database Literature Search ......................................................... 26
Hand Searches .............................................................................................. 28
Update Searches ........................................................................................... 28
Management of References ...................................................................................... 28
Assessment of Papers for Eligibility ........................................................................ 28
Data Extraction ........................................................................................................ 28
Assessment of Study Validity ................................................................................. 29
Quality of the Body of Evidence ............................................................................ 32
Synthesis of Results ................................................................................................ 32
Peer Review ............................................................................................................ 32

Chapter 3. Results ............................................................................................................... 33
Studies Meeting Eligibility Criteria ........................................................................ 33
1. Does HBOT improve mortality and morbidity in patients who have
traumatic brain injury or nontraumatic brain injury, such as anoxic ischemic
encephalopathy? ............................................................................................... 33
Traumatic Brain Injury ..................................................................................... 33
Controlled Trials ........................................................................................ 33
Observational Studies .................................................................................. 36
Abstract and Conference Proceedings ........................................................ 39
Other Nontraumatic Brain Injury ...................................................................... 39
Controlled Trials ........................................................................................ 39
Observational Studies .................................................................................. 40
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Abstract and Conference Proceedings ........................................................ 40
Synthesis .......................................................................................................... 41
2. Does HBOT improve functional outcomes in patients who have
cerebral palsy? .................................................................................................. 41
Controlled Trials .............................................................................................. 41
Observational Studies ...................................................................................... 43
Abstract and Conference Proceedings ............................................................. 43
Synthesis .......................................................................................................... 44
3. Does HBOT improve mortality and morbidity in patients who have suffered
a stroke? ........................................................................................................... 44
Controlled Trials .............................................................................................. 44
Observational Studies ...................................................................................... 47
Abstract and Conference Proceedings ............................................................. 49
Synthesis .......................................................................................................... 49
4. What are the adverse effects of using HBOT in brain injury, cerebral palsy,
or stroke patients? ........................................................................................... 50
Neurological Complications ........................................................................... 50
Pulmonary Complications ............................................................................... 51
Ear Problems ................................................................................................... 52
Quality of Evidence about Adverse Events .................................................... 52

Chapter 4. Conclusions ..................................................................................................... 59

Chapter 5. Future Research ............................................................................................... 61
Outcomes Studies .............................. ................................................................... 69
Studies of Diagnostic Tests and Intermediate Outcome Measures ........................ 63

References .......................................................................................................................... 65

Evidence Table 1. Brain Injury Controlled Trial Data ........................................................ 75

Evidence Table 2. Brain Injury Observational Study Data .................................................. 81

Evidence Table 3. Cerebral Palsy Controlled Trial Data ..................................................… 99

Evidence Table 4. Cerebral Palsy Observational Study Data ............................................. 103

Evidence Table 5. Stroke Controlled Trial Data .................................................................. 109

Evidence Table 6. Stroke Observational Study Data ........................................................... 118

Evidence Table 7. Conference Proceedings and Abstract-only Study Data ........................ 139

Evidence Table 8. Quality Assessment of Controlled Studies ............................................ 163

Evidence Table 9. Quality Assessment of Observational Studies ....................................... 172
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Bibliography .....................................................................................................................….191

Appendix A. Indications for HBOT .................................................................................... 231

Appendix B. Research Team, Technical Expert Advisory Group, and Peer Reviewers ..... 233

Appendix C. Literature Search Strategies ......................................................................…. 238

Appendix D. Quality Assessment Criteria ........................................................................... 242

Appendix E. Excluded Studies .........................................................................................… 245

Appendix F. Studies with Intermediate Outcomes ..........................................................…. 251

Appendix G. Unretrieved Studies ....................................................................................….. 253

Appendix H. Outcome Measures Used in HBOT Studies ................................................… 255

Abbreviations and Acronyms .........................................................................................…. 258

Glossary of Terms ..........................................................................................................….. 260

Supplement. A Qualitative Assessment of Brain Injury, Cerebral Palsy, and Stroke
Patient, Caregiver and Clinician Values of Outcomes .....................................................…. 263

Figures

Figure 1. HBOT Literature search results ..................................................................... 53
Figure 2. Study Design Algorithm ................................................................................ 54

Tables

Table 1. Glasgow Coma Scale ...................................................................................... 15
Table 2. Results for Study by Artu, Chacornac, and Deleuze ...................................... 34
Table 3. Results of Study by Rockswold, Ford, et al .................................................... 34
Table 4. Controlled Trials of HBOT in Brain Injury .................................................... 55
Table 5. Controlled Trials of HBOT in Cerebral Palsy................................................. 56
Table 6. Controlled Trials of HBOT in Stroke ............................................................. 57
ix
Agency for Healthcare Research and Quality
Evidence Report/Technology Assessment
Number 85
Hyperbaric Oxygen Therapy for Brain Injury,
Cerebral Palsy, and Stroke
Summary
Overview physical functioning. Cerebral palsy refers to a
motor deficit that usually manifests itself by 2
Hyperbaric oxygen therapy (HBOT) is the years of age and is secondary to an abnormality of
inhalation of 100 percent oxygen inside a at least the part of the brain that relates to motor
hyperbaric chamber that is pressurized to greater function. Stroke refers to a sudden interruption of
than 1 atmosphere (atm). HBOT causes both the blood supply to the brain, usually caused by a
mechanical and physiologic effects by inducing a blocked artery or a ruptured blood vessel, leading
state of increased pressure and hyperoxia. HBOT to an interruption of homeostasis of cells, and
is typically administered at 1 to 3 atm. While the symptoms such as loss of speech and loss of motor
duration of an HBOT session is typically 90 to function.
120 minutes, the duration, frequency, and
While these conditions have different etiologies,
cumulative number of sessions have not been
prognostic factors, and outcomes, they also have
standardized.
important similarities. Each condition represents
HBOT is administered in two primary ways, a broad spectrum, from barely perceptible or mild
using a monoplace chamber or a multiplace disabilities to devastating ones. All three are
chamber. The monoplace chamber is the less- characterized by acute and chronic phases and by
costly option for initial setup and operation but changes over time in the type and degree of
provides less opportunity for patient interaction disability. Another similarity is that the outcome
while in the chamber. Multiplace chambers allow of conventional treatment is often unsatisfactory.
medical personnel to work in the chamber and For brain injury in particular, there is a strong
care for acute patients to some extent. The entire sense that conventional treatment has made little
multiplace chamber is pressurized, so medical impact on outcomes.
personnel may require a controlled decompression,
Predicting the outcome of brain injury, cerebral
depending on how long they were exposed to the
palsy, and stroke is difficult. Prognostic
hyperbaric air environment.
instruments, such as the Glasgow Coma Scale
The purpose of this report is to provide a guide (GCS) for brain injury, are not precise enough to
to the strengths and limitations of the evidence reliably predict an individual patient’s mortality
about the use of HBOT to treat patients who have and long-term functional status. Various
brain injury, cerebral palsy, and stroke. Brain prognostic criteria for the cerebral palsy patient’s
injury can be caused by an external physical force function have been developed over the years. For
(also known as traumatic brain injury, or TBI); example, if a patient is not sitting independently
rapid acceleration or deceleration of the head; when placed by age 2, then one can predict with
bleeding within or around the brain; lack of approximately 95 percent confidence that he/she
sufficient oxygen to the brain; or toxic substances never will be able to walk. However, it is not
passing through the blood-brain barrier. Brain possible to predict precisely when an individual
injury results in temporary or permanent patient is likely to acquire a particular ability, such
impairment of cognitive, emotional, and/or
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES • Public Health Service
as smiling, recognizing other individuals, or saying or • Population. Patients with:
understanding a new word. o brain injury from any cause and in any stage (acute,
Mortality and morbidity from a stroke are related to older subacute, or chronic).
age, history of myocardial infarction, cardiac arrhythmias, o cerebral palsy of any etiology.
diabetes mellitus, and the number of stroke deficits. Functional o thrombotic stroke.
recovery is dependent on numerous variables, including age,
• Outcomes. We sought articles reporting any clinical
neurologic deficit, comorbidities, psychosocial factors,
endpoint. We focused on health outcomes, including
educational level, vocational status, and characteristics of the
mortality and functional changes that a patient would
stroke survivor’s environment.
experience, rather than intermediate outcomes.
The report focuses on the quality and consistency of studies Intermediate outcomes include physiologic measures, such
reporting clinical outcomes of the use of HBOT in humans as intracranial pressure, cerebrospinal fluid lactate levels, or
who have brain injury, cerebral palsy, or stroke. This changes in cerebral blood flow, or results of imaging
information can be used to help providers counsel patients who studies. Some clinical measures, such as neuropsychiatric
use this therapy and to identify future research needs. and cognitive tests, are also intermediate measures. We did
not assume that any of these intermediate measures of the
Reporting the Evidence
effect of HBOT on patients with brain injury, cerebral
This review addresses the following questions: palsy, or stroke was proven to be an indicator of the long-
term outcome. Instead, in reviewing articles for inclusion
1. Does HBOT improve mortality and morbidity in patients
in this report, we were particularly interested in studies that
who have traumatic brain injury or nontraumatic brain
reported both intermediate measures and health outcomes,
injury, such as anoxic ischemic encephalopathy?
to assess the strength of evidence about their correlation.
2. Does HBOT improve functional outcomes in patients who
• Design. We included original studies of human subjects
have cerebral palsy? (Examples of improved functional
that reported original data (no reviews). All study designs
outcomes are decreased spasticity, improved speech,
except for case reports and small case series were eligible for
increased alertness, increased cognitive abilities, and
inclusion. Before-after or time-series studies with no
improved visual functioning.)
independent control group were included if a) five or more
3. Does HBOT improve mortality and morbidity in patients
cases were reported, and b) outcome measures were
who have suffered a stroke?
reported for both the pre- and post-HBOT period.
4. What are the adverse effects of using HBOT in these
conditions? Methodology
To identify the patient groups, interventions, and outcomes
that should be included in the review, we read background Technical Expert Advisory Group (TEAG)
material from diverse sources including textbooks, government
We identified technical experts to assist us in formulating the
reports, proceedings of scientific meetings, and Web sites. We
research questions and identifying relevant databases for the
also conducted focus groups and interviews to improve our
literature search. The expert panelists included a neurologist
understanding of the clinical logic underlying the rationale for
specializing in stroke, a neurosurgeon specializing in severe
the use of HBOT. In the focus groups, we identified outcomes
brain injury, a pediatric neurologist with expertise in treating
of treatment with HBOT that are important to patients,
patients with cerebral palsy, and a physician with an HBOT
caregivers, and clinicians and examined whether patients,
practice. Throughout the project period, we consulted
caregivers, and clinicians who have experience with HBOT
individual members of the TEAG on issues that arose in the
value certain outcomes differently from those who have not
course of identifying and reviewing the literature.
used HBOT. A broader goal of the focus groups was to better
understand the disagreement between supporters and non- Literature Search, Study Selection, and Data
supporters of HBOT. Extraction
The following interventions, populations, outcomes, and We searched a broad range of databases to identify published
study design criteria were used to formulate the literature search and unpublished studies of the effectiveness and harms of
strategy and to assess eligibility of studies. HBOT in patients with brain injury, cerebral palsy, and stroke.
• Intervention. Hyperbaric oxygen therapy: any treatment Each database was searched from its starting date to March
using 100 percent oxygen supplied to a patient inside a 2001. The databases searched were:
hyperbaric chamber that is pressurized to greater than 1 • MEDLINE®
atm.
• PreMEDLINE®
2