Hyperbaric Oxygen Therapy for Brain Injury, Cerebral Palsy, and Stroke

Agency for Healthcare Research and Quality

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• Fair: Generally comparable groups assembled initially (inadequate or unstated randomization and concealment methods) but some question remains whether some (although not major) differences occurred with followup; measurement instruments acceptable (although not the best) and generally applied equally; outcome assessment masked; some, but not all, important outcomes considered; appropriate attention to some, but not all, potential confounders; for RCTs, intention-to-treat analysis.
• Poor: Groups assembled initially not close to being comparable or not maintained throughout the study; measurement instruments unreliable or invalid or not applied equally among groups; outcome assessment not masked; key confounders given little or no attention; for RCTs, no intention-to-treat analysis.

For each study, the reviewer’s assessment of external validity is given, including an assessment of the evidence that the study population reflects the underlying patient population (agerange, co-morbidities, co-interventions, etc.). External validity indicates the applicability of the results of the study to clinical practice. For example, if the study recruited a narrowly defined group of patients, the results may not be generalizable to a broader spectrum of patients. A study can have high internal validity but low external validity. There are no well-defined criteria for assessing external validity, and clinicians must assess the applicability of the results to the patient population for which the intervention is intended.

Findings

Brain Injury

• For traumatic brain injury, one randomized trial provided fair evidence that HBOT might reduce mortality or the duration of coma in severely injured TBI (traumatic brain injuries) patients. However, in this trial, HBOT also increased the chance of a poor functional outcome. A second fair quality randomized trial found no difference in mortality or morbidity overall, but a significant reduction in mortality in one subgroup. Therefore, they provide insufficient evidence to determine whether the benefits of HBOT outweigh the potential harms.
• The quality of the controlled trials was fair, meaning that deficiencies in the design add to uncertainty about the validity of results.
• Due to flaws in design or small size, the observational studies of HBOT in TBI do not establish a clear, consistent relationship between physiologic changes after HBOT sessions and measures of clinical improvement.
• The evidence for use of HBOT in other types of brain injury is inconclusive. No good- or fair quality studies were found.

Cerebral Palsy

• There is insufficient evidence to determine whether the use of HBOT improves functional outcomes in children with 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. As both groups improved, the benefit of pressurized air and of HBOT at 1.3 to 1.5 atm should both be examined in future studies.
• The only other controlled study compared HBOT treatments with 1.5 atm to delaying treatment for 6 months. As in the placebo-controlled study, significant improvements were seen, but there was not a significant difference between groups.
• Two fair-quality uncontrolled studies (one time-series, one before-after) found improvements in functional status comparable to the degree of improvement seen in both groups in the controlled trial.
• Although none of the studies adequately measured caregiver burden, study participants often noted meaningful reductions in caregiver burden as an outcome of treatment.

Stroke

• Although a large number of studies address HBOT for the treatment of stroke, the evidence is insufficient to determine whether HBOT reduces mortality in any subgroup of stroke patients because no controlled trial assessed was designed to assess mortality.
• Among controlled trials, the evidence about morbidity is conflicting. The three best-quality trials found no difference in neurological measures in patients treated with HBOT versus patients treated with pressurized room air.
• Two other controlled trials, one randomized and one nonrandomized, found that HBOT improved neurological outcomes on some measures. However, both were rated poor-quality.
• Most observational studies reported favorable, and sometimes dramatic, results, but failed to prove that these results can be attributed to HBOT. For example, one retrospective study found better mortality rates in patients who received HBOT than a comparison group of patients from a different hospital who did not. The study did not provide information on mortality rates from other causes in each hospital; this information would have made it easier to judge whether the improved survival was due to HBOT or to differences in overall quality of care at the HBOT hospital.
• The observational studies of HBOT provided insufficient evidence to establish a clear relationship between physiologic changes after HBOT sessions and measures of clinical improvement. Few studies established that patients were stable at baseline.

Adverse Events
 

• 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.
• The few data that are available from controlled trials and cohort studies of TBI suggest that the risk of seizure may be higher in patients with brain injuries treated with HBOT.
• No study of HBOT for brain injury, cerebral palsy, or stroke has been designed to identify the chronic neurologic complications.
• Pulmonary complications were relatively common in the trials of brain-injured patients. There are no reliable data on the incidence of aspiration in children treated for cerebral palsy with hyperbaric oxygen.
• Ear problems are a known potential adverse effect of HBOT. While ear problems were reported in brain injury, cerebral palsy, and stroke studies the incidence, severity and effect on outcome are not clear. However, the rates reported among cerebral palsy patients were higher (up to 47 percent experiencing a problem) than reported with brain injury or stroke. However, the data in brain injury are limited by the use of prophylactic myringotomies.

Supplemental Qualitative Analysis

• Opinions about the frequency and severity of risks of HBOT vary widely.