Hyperbaric Oxygen for Lower Limb Trauma (HOLLT): an international multi-centre randomised clinical trial

Abstract

Introduction: Hyperbaric oxygen treatment (HBOT) is sometimes used in the management of open fractures and severe soft tissue crush injury, aiming to reduce complications and improve outcomes.

Methods: Patients with open tibial fractures were randomly assigned within 48 hours of injury to receive standard trauma care or standard care plus 12 sessions of HBOT. The primary outcome was the incidence of necrosis or infection or both occurring within 14 days of injury.

Results: One-hundred and twenty patients were enrolled. Intention to treat primary outcome occurred in 25/58 HBOT assigned patients and 34/59 controls (43% vs 58%, odds ratio (OR) 0.55, 95% confidence interval (CI) 0.25 to 1.18, P = 0.12). Tissue necrosis occurred in 29% of HBOT patients and 53% of controls (OR 0.35, 95% CI 0.16 to 0.78, P = 0.01). There were fewer late complications in patients receiving HBOT (6/53 vs 18/52, OR 0.22, 95% CI 0.08 to 0.64, P = 0.007) including delayed fracture union (5/53 vs 13/52, OR 0.31, 95% CI 0.10 to 0.95, P = 0.04). Quality of life measures at one and two years were superior in HBOT patients. The mean score difference in short form 36 was 2.90, 95% CI 1.03 to 4.77, P = 0.002, in the short musculoskeletal function assessment (SMFA) was 2.54, 95% CI 0.62 to 4.46, P = 0.01; and in SMFA daily activities was 19.51, 95% CI 0.06 to 21.08, P = 0.05.

Conclusions: In severe lower limb trauma, early HBOT reduces tissue necrosis and the likelihood of long-term complications, and improves functional outcomes. Future research should focus on optimal dosage and whether HBOT has benefits for other injury types.

Keywords: Fractures; Hyperbaric oxygen treatment; Injuries; Musculo-skeletal; Orthopaedics; Outcome; Wounds.

Conflict of interest statement

Conflicts of interest and funding:

The study received funding from Australia’s National Health and Medical Council (NHMRC Project Grant 49096) and from the Victorian Trauma Foundation (Project Grant NV12), providing for project management, the operation of the data centre plus some partial support for data collection. The involvement of the Hobart site was made possible by a grant from the Tasmanian Motor Accident Insurance Board Injury Prevention Foundation.

Belinda Gabbe was supported by an Australian Research Council Future Fellowship and Paul Myles held an NHMRC Practitioner Fellowship.

All other study related costs and all clinical care and hyperbaric oxygen therapy costs were provided from within the budgets of each participating institution.

The funding sources had no role in the study design, conduct, analysis, writing or submission for publication. There were no commercial entities or interests involved in the trial. There are no identified conflicts of interest for any of the authors regarding the conduct and reporting of this study.

Data access

The Principal Investigator, Ian Millar, and the Project Manager, Rosemary McGinnes, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. The Principal Investigator only gained access to the site raw data entries and group allocation after data entry closed and data were extracted from the Web Entry Data System for transmission to the study statisticians for analysis. Most statistical analyses were performed by Catherine Martin, with patient reported outcome data analysed by Belinda Gabbe.

Transparency statement

As Principal Investigator, first author and guarantor, Ian Millar affirms that the manuscript is honest, accurate and a transparent account of the study being reported, with no important aspects omitted and discrepancies from original plans reported and explained within the manuscript.

Data sharing

A file of de-identified patient data can be made available to researchers upon reasonable request, subject to a research plan being communicated to the HOLLT investigators with assurance of the identity and credentials of the requesting researcher(s). This file includes de-identified data extracted from the HOLLT study Web Entry Data System and the results of arbitrated outcomes for each of the 120 study participants.

Monash University holds an archive of all study information, raw data and image files. This is de-identified healthcare data which is re-identifiable via the international collaborators and cannot be released due to privacy requirements and trial agreements between Monash University and the study collaborators. It was, however, envisaged that future researchers might wish to conduct further analyses based upon these data, by entering into a confidentiality agreement with the HOLLT investigators and obtaining Human Research Ethics approval from The Alfred and Monash Ethics Committee and the HOLLT collaborator group.

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