Millar IL, Lind FG, Jansson KÅ, Hájek M, Smart DR, Fernandes TD, McGinnes RA, Williamson OD, Miller RK, Martin CA, Gabbe BJ, Myles PS, Cameron PA, HOLLT investigator group, et al.
Diving and hyperbaric medicine. Date of publication 2022 Sep 30;volume 52(3):164-174.
1. Diving Hyperb Med. 2022 Sep 30;52(3):164-174. doi: 10.28920/dhm52.3.164-174.
Hyperbaric Oxygen for Lower Limb Trauma (HOLLT): an international multi-centre
randomised clinical trial.
Millar IL(1)(2)(3), Lind FG(4), Jansson KÅ(5), Hájek M(6)(7), Smart DR(8)(9),
Fernandes TD(10), McGinnes RA(2), Williamson OD(2), Miller RK(11), Martin CA(2),
Gabbe BJ(12)(13), Myles PS(14), Cameron PA(12); HOLLT investigator group.
Author information:
(1)Department of Intensive Care and Hyperbaric Medicine, Alfred Health,
Melbourne, Victoria, Australia.
(2)Department of Epidemiology and Preventive Medicine, School of Public Health
and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
(3)Corresponding author: Dr Ian Millar, The Alfred Hyperbaric Service, PO Box
315, Prahran, Victoria 3181, Australia, i.millar@alfred.org.au.
(4)Department of Physiology and Pharmacology, Section for Anesthesiology and
Intensive Care Medicine, Karolinska Institutet at Karolinska University
Hospital, Stockholm, Sweden.
(5)Department of Molecular Medicine and Surgery, Karolinska Institutet at
Karolinska University Hospital, Stockholm, Sweden.
(6)Centre of Hyperbaric Medicine, Ostrava City Hospital, Ostrava, Czech
Republic.
(7)Department of Biomedical Sciences, Faculty of Medicine, University of
Ostrava, Ostrava-Zabreh, Czech Republic.
(8)Department of Diving and Hyperbaric Medicine, Royal Hobart Hospital, Hobart,
Tasmania, Australia.
(9)School of Medicine, University of Tasmania, Tasmania, Australia.
(10)Hyperbaric Medicine Unit, Department of Anesthesia, Hospital Pedro Hispano,
Matosinhos, Portugal.
(11)Department of Orthopaedic Surgery, Alfred Health, Mebourne, Victoria,
Australia.
(12)Prehospital, Emergency and Trauma Research Unit, Department of Epidemiology
and Preventive Medicine, School of Public Health and Preventive Medicine, Monash
University, Melbourne, Victoria, Australia.
(13)Health Data Research UK, Swansea University, Swansea, United Kingdom.
(14)Department of Anaesthesiology and Perioperative Medicine, Alfred Health and
Monash University, Melbourne, Victoria, Australia.
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.
Copyright: This article is the copyright of the authors who grant Diving and
Hyperbaric Medicine a non-exclusive licence to publish the article in electronic
and other forms.
DOI: 10.28920/dhm52.3.164-174
PMCID: PMC9536848
PMID: 36100927 [Indexed for MEDLINE]
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.
