Adjuvant hyperbaric oxygen therapy in trauma

The physiological role of adjuvant hyperbaric oxygen therapy in
trauma management and rehabilitation
A systematic review of the literature comparing the therapeutic uses of
hyperbaric oxygen therapy in trauma beyond its’ original clinical application
interstitial pressure rises, compressing
Major trauma is a devastating health
problem, accounting for 20,000 hospital
low pressure venous outflow,
accentuating further oedema.
admissions and 5,400 deaths in
Vasogenic oedema increases cellular
England alone1. Mortality and morbidity
oxygen diffusion distances,
mainly result from diminished perfusion
compromising perfusion and creating
caused by damaged vasculature, and
localised oedematous hypoxia.
increased cellular oxygen demand
Significant hypoxia causes depletion of
which combine to create severe oxygen
aerobically dependent ATP stores (see
debt. The resultant hypoxia presents a
figure 1). The absence of ATP causes
major difficulty in trauma management,
intracellular sodium pumps to fail
where the reductions of these effects
resulting in intracellular sodium build-up
are a priority.
with accompanying potassium and
Pathophysiology of trauma
chloride influx. The additional osmotic
Direct trauma to vasculature and
lymphatics cause fluid accumulation in
the interstitium. Inflammatory pathways
activated by the traumatic insult
increase capillary permeability, causing
vasogenic oedema in the interstitial
space3. With the expanding fluid,
The physiological role of adjuvant hyperbaric
Oxygen therapy in trauma management
and rehabilitation
By John Millwood Hargrave
Figure 1. Illustration of sodium potassium pump
Edited by LIME Research Editor 1 | P a g e
pressure this causes increases
ATA), the diffusion distance oxygen can
cytogenic oedema and creates a vicious
accomplish is trebled. The physiological
cycle of oedematous hypoxia on already
relevance is that oedematous hypoxic
ischaemic tissue4.
tissues can receive oxygen at diffusion
distances greater than normobaric
Hyperbaric oxygenation
Hyperbaric oxygenation (HBO2T) occurs
when the patient breathes in 100%
oxygen (O2) at pressures exceeding
High partial pressures of oxygen
exceeding 500 mmHg causes
vasoconstriction, mainly of the arteries,
increasing venous outflow relative to
that of the atmosphere3. High
concentration oxygen at atmospheric
level, and localised exposure of affected
arterial inflow. This decreases capillary
transudation into the interstitium, and so
decreases oedema. There is also an
limbs to oxygen does not qualify as
hyperbaric oxygenation, so are excluded
approximate 20% decrease in limb
blood loss, with the decreased blood
in this review.
supply offset by increased oxygen
Physiological rationale for HBO2T
Enhanced cellular function7
Hyperoxia promotes angiogenesis and
HBO2T promotes the reversal of the
stimulates fibroblast and collagen
pathophysiology of trauma via the
synthesis, enhancing healing. HBO2T
following mechanisms:
therapy has also been shown to
Increased oxygen diffusion
enhance aerobic leucocyte activity,
The distance of oxygen diffusion
which reduces the common
through fluid is proportional to the
complication of infection in trauma.
square root of oxygen concentration in
the capillary. At 2 times the atmospheric
Current and future indications
pressure (2
The physiological role of adjuvant hyperbaric
Oxygen therapy in trauma management
and rehabilitation
By John Millwood Hargrave
Edited by LIME Research Editor 2 | P a g e
The current indications for HBO2T use
are under constant review by the
Undersea and Hyperbaric Medical
Society (UHMS) as new evidence
emerges for future indications. Its
current recommended uses as of
UHMS, 20118 are shown in Box 1.
This review will focus on the following
recommended indications:
Compartment syndrome, thermal burns,
acute blood loss, fracture healing and
traumatic brain injury.
UHMS 2011 indications for hyperbaric
Compression sickness
Carbon monoxide poisoning
Air or gas embolism
Idiopathic sudden sensorineural
hearing loss
Crush injury
Compartment syndrome
Gas gangrene
Thermal burns
Healing of problematic wounds and
compromised skin grafts and flaps
Acute blood loss
Necrotising soft tissue infection
Refractory osteomyelitis
Radiation injury (soft tissue and bony
Box 1
Preliminary reading and discussion of
the subject was conducted at the
Hyperbaric Medical Facility, Isle of Man9
(IOM) and the Keyll Darree Medical
Library at Nobles Hospital, IOM. The
review was conducted through the
University of Liverpool website using
Scopus, PubMed and Discover
Randomised controlled studies were
preferred and where unavailable, nonrandomised controlled, observational
and case report studies were included.
Rationale, review of clinical evidence and discussion for adjuvant HBO2T in
Compartment syndrome
Following trauma, pressures in skeletal muscles may rise sufficiently to cause vascular
stasis, resulting in oedematous hypoxia and ischaemia. If interstitial pressure rise over
The physiological role of adjuvant hyperbaric
Oxygen therapy in trauma management
and rehabilitation
By John Millwood Hargrave
Edited by LIME Research Editor 3 | P a g e
30mmHg, a Fasciotomy is performed to relieve pressure and restore tissue perfusion10.
HBO2T is therefore physiologically indicated due to its anti-oedematous and
hyperoxygenative properties.
Prompt HBO2T therapy being effectively used to control post-surgical intracompartmental calf pressures exceeding 35 mmHg11; this effect was also noted despite
intra-operative hypotension also being reported, suggesting, although an isolated event,
that HBO2T therapy may be effective in sub-adequate blood flow. A further case series12
identified 10 patients who recovered with Fasciotomies following symptomatic
compartment syndrome from compartment pressures ranging between 15-48 mmHg.
It is not suggested by the UHMS that HBO2T should replace fasciotomy is clinically
established cases. However if HBO2T is used prophylactically, in situations where
compartment syndrome is a risk, such as surgery, it may reduce the incidence of postoperative compartment syndrome. As yet no trials have been conducted into this clinical
indication, but this suggests a direction for future research.
Thermal burns
Burns activate the inflammatory cascade, causing vasodilation and increased vascular
permeability. This fluid shift from intravascular to extravascular spaces causes
hypovolaemia and localised oedema. It is therefore an indication to use HBO 2T,due to
its vasoconstrictive and antioedematous actions.
A retrospective study13 found that the length of hospital stay in 16 patients with between
18-39% burns was significantly reduced from 33 days in the control group (n=8) to 21
days in the adjuvant HBO2T group (n=8) (p=0.05). 24 patients with 40-80% burns
receiving adjuvant HBO2T therapy required half the number of operations (4 vs 8)
compared to those receiving only the standard treatment14.
The physiological role of adjuvant hyperbaric
Oxygen therapy in trauma management
and rehabilitation
By John Millwood Hargrave
Edited by LIME Research Editor 4 | P a g e
While these results are encouraging, unless HBO2T services become incorporated in
burns centres, the risk of moving critically ill patients from major burns units, where their
clinical need is greatest, to hyperbaric chambers is likely to be too great.
Managing blood loss remains the foremost challenge in trauma. Decreasing blood
stocks, autoimmune rejection and disease transmission risk creates a need for
alternatives. The hyperoxygenating and vasoconstrictive effect of HBO2T as a
temporalising measure for hypoxic tissue is an interesting direction.
A randomised controlled trial15 of HBO2T use on 41 patients with haemoglobin levels
<90 g/L found that 30% increased their levels of hepatic venous oxygen saturation
(ShvO2). Serum lactate levels were also significantly decreased, which reflects
decreased anaerobic respiration.
These results are encouraging, and suggest that HBO2T could be used as an adjuvant
to minimise blood transfusions, or even replace transfusions in non-critical scenarios of
blood loss. However until facilities are in place to safely treat actively haemorrhaging
patients in hyperbaric chambers, blood transfusions will still be favoured.
The treatment of fractures centres on re-establishing the structural integrity of bone, and
restoring function to the traumatised area. Fracture healing is impaired by poor
vascularity, infection and loss of soft tissues18. As already discussed, the potential for
HBO2T therapy in promoting angiogenesis, enhancing leukocyte function and promoting
soft tissue repair makes it an interesting adjuvant therapy for fractures.
There a paucity of clinical trials carried out on humans with HBO2T in fractures. A recent
study has found an increased production of bone morphogenic cytokines involved in
fracture healing19, which is encouraging. While these trials suggest potential in HBO2T
The physiological role of adjuvant hyperbaric
Oxygen therapy in trauma management
and rehabilitation
By John Millwood Hargrave
Edited by LIME Research Editor 5 | P a g e
therapy, the lack of randomised trials
conducted on humans is limiting. There are
currently three ongoing randomised
controlled trials21-23 to investigate HBO2T
therapy in fracture healing. Until these are
complete, there is insufficient clinical
evidence to support or disprove the
CBF - Cerebral brain function,
HBOT – Hyperbaric Oxygen Therapy
Figure 2
treatment of fractures with HBO2T.
Traumatic brain injury
The brain consumes 20% of total systemic oxygen, and, due to few energy reserves, is
dependent on a good oxygen and glucose supply. It is therefore most vulnerable to
hypoxia secondary to a traumatic brain injury (TBI). While no effective treatment for TBI
exist, managing secondary brain injury is essential to reducing mortality and morbidity.
Secondary injury involves tissue hypoxia, inflammation and resulting cerebral oedema.
HBO2T has been shown to be effective in high altitude cerebral oedema 24, and the
ability of HBO2T to correct tissue hypoxia, inflammation and therefore cerebral oedema
makes it an interesting
and exciting adjuvant therapy for prevention of secondary TBI.
These studies demonstrate the impact HBO2 therapy can have on reducing mortality
and morbidity. Going forward, a recent trial27 has demonstrated HBO2T inducing
significant brain function improvements, as seen in Figure 2, in 56 patients following
mild TBI.
Side-effects and contraindications of HBO2T
The side effect profile of HBO2T means it should not be treated as completely benign.
The most common complications are middle ear barotrauma due to fluctuating
atmospheric pressure. Cerebral oxygen toxicity is a rare (incidence due to HBO 2T are
The physiological role of adjuvant hyperbaric
Oxygen therapy in trauma management
and rehabilitation
By John Millwood Hargrave
Edited by LIME Research Editor 6 | P a g e
1.3/10,000) but potentially serious complication. However, if rates of decompression are
prolonged and strictly controlled, then this risk can almost be reduced to almost zero 28.
The only absolute contraindication is an untreated pneumothorax. Where there is
polytrauma, particularly including the chest, pneumothorax must be ruled out or treated
before HBO2T. If a chest drain is correctly inserted, the risk is reduced to almost zero28.
Conclusion and areas for future research
The evidence for adjuvant HBO2T is compelling at this early stage, suggesting it has a
future role in trauma management and rehabilitation.
This review makes no attempt to specify ideal timings or pressures for treating the
individual traumatic insults discussed. In the studies, the specific pressures either were
not recorded or conflicted between studies, so few inferences of optimal hyperbaric
regimen could not be discerned. This is an essential direction for future research, as the
diverse clinical indications may have differing optimal pressures.
The review does not apply any economic evaluation to HBO2T. Any future research into
efficacy and cost effectiveness are essential in assessing HBO2T viability.
Further information regarding HBO2T in the UK is available from the British Hyperbaric
Association at
The physiological role of adjuvant hyperbaric
Oxygen therapy in trauma management
and rehabilitation
By John Millwood Hargrave
Edited by LIME Research Editor 7 | P a g e
Bozzette A, Aeron-Thomas A. Reducing trauma deaths in the UK. Lancet
Mathieu D. Role of hyperbaric oxygen therapy in the management of lower
extremity wounds. Int J Low Extrem Wounds 2006;5(4):233-5.
Buettner MF, Wolkenhauer D. Hyperbaric oxygen therapy in the treatment of
open fractures and crush injuries. Emerg Med Clin North Am 2007;25(1):177-88.
Myers RA. Hyperbaric oxygen therapy for trauma: crush injury, compartment
syndrome, and other acute traumatic peripheral ischemias. Int Anesthesiol Clin
JYS B. Hyperbaric oxygen therapy in reimplantation of severed limbs: A report of
34 cases. Proceedings of the eighth international conference on hyperbaric
medicine 1987:182-6.
Hills BA. A role for oxygen-induced osmosis in hyperbaric oxygen therapy. Med
Hypotheses 1999;52(3):259-63.
Rowe K. Hyperbaric oxygen therapy: what is the case for its use? J Wound Care
Society UaHM. Indications for Hyperbaric Oxygen therapy - 2011. 2011. (accessed 01/04/2014).
STB W. The role of hyperbaric oxygen therapy in trauma. Trauma 2010;12:1320.
Masquelet AC. Acute compartment syndrome of the leg: pressure measurement
and fasciotomy. Orthop Traumatol Surg Res 2010;96(8):913-7.
Van Poucke S, Leenders T, Saldien V, Verstreken J, Beaucourt L, Adriaensen H.
Hyperbaric oxygen (HBO) as useful, adjunctive therapeutic modality in
compartment syndrome. Acta Chir Belg 2001;101(2):73-4.
al HGe. Hyperbaric oxygen and skeletal muscle compartment syndrome.
Contemporary Orthopaedics 1989;18:167-74.
The physiological role of adjuvant hyperbaric
Oxygen therapy in trauma management
and rehabilitation
By John Millwood Hargrave
Edited by LIME Research Editor 8 | P a g e
Cianci P, Lueders HW, Lee H, Shapiro RL, Sexton J, Williams C, et al. Adjunctive
hyperbaric oxygen therapy reduces length of hospitalization in thermal burns. J
Burn Care Rehabil 1989;10(5):432-5.
Cianci P LH, Lee H et al. Adjuvant hyperbaric oxygen reduces the need for
surgery in 40-80% burns. Journal of Hyperbaric Medicine 1988;3:97.
Ueno S, Sakoda M, Kurahara H, Iino S, Minami K, Ando K, et al. Safety and
efficacy of early postoperative hyperbaric oxygen therapy with restriction of
transfusions in patients with HCC who have undergone partial hepatectomy.
Langenbecks Arch Surg 2011;396(1):99-106.
Wright JK, Ehler W, McGlasson DL, Thompson W. Facilitation of recovery from
acute blood loss with hyperbaric oxygen. Arch Surg 2002;137(7):850-3.
Necas E, Neuwirt J. Response of erythropoiesis to blood loss in hyperbaric air.
Am J Physiol 1969;216(4):800-3.
Fong K, Truong V, Foote CJ, Petrisor B, Williams D, Ristevski B, et al. Predictors
of nonunion and reoperation in patients with fractures of the tibia: an
observational study. BMC Musculoskelet Disord 2013;14:103.
Barth E, Sullivan T, Berg E. Animal model for evaluating bone repair with and
without adjunctive hyperbaric oxygen therapy (HBO): comparing dose schedules.
J Invest Surg 1990;3(4):387-92.
Ueng SW, Lee SS, Lin SS, Wang CR, Liu SJ, Yang HF, et al. Bone healing of
tibial lengthening is enhanced by hyperbaric oxygen therapy: a study of bone
mineral density and torsional strength on rabbits. J Trauma 1998;44(4):676-81.
IL M. NCT00264511 - Does hyperbaric oxygen reduce complications and
improve outcomes after open tibial fractures with severe soft tissue injury? An
interntional multi-centre randomized comtrolled trial. Hyperbaric Service, Alfred
Hospital, Melbourne, Australia; 2006.
Knobe M MS. NCT01264146 - Hyperbaric oxygen therapy in calcaneal fractures:
Can it decrease the soft-tissue complication rate? (HOCIF). Department of
Orthopaedic Trauma, RWTH Aachen University, Aachen, Germany; 2011.
The physiological role of adjuvant hyperbaric
Oxygen therapy in trauma management
and rehabilitation
By John Millwood Hargrave
Edited by LIME Research Editor 9 | P a g e
M K. NCT01365780 - Hyperbaric oxygen therapy in distal radius fractures: Can it
shorten recovery time and increase fracture healing? (HBOTRadius). Department
of Orthopedic Trauma, Aachen University, Aachen, Germany; 2011.
Hackett PH, Roach RC. High altitude cerebral edema. High Alt Med Biol
Golden Z, Golden CJ, Neubauer RA. Improving neuropsychological function after
chronic brain injury with hyperbaric oxygen. Disabil Rehabil 2006;28(22):137986.
Golden ZL, Neubauer R, Golden CJ, Greene L, Marsh J, Mleko A. Improvement
in cerebral metabolism in chronic brain injury after hyperbaric oxygen therapy. Int
J Neurosci 2002;112(2):119-31.
Ren H, Wang W, Ge Z. Glasgow Coma Scale, brain electric activity mapping and
Glasgow Outcome Scale after hyperbaric oxygen treatment of severe brain
injury. Chin J Traumatol 2001;4(4):239-41.
Davis JC DJ, Heimbach RD. Hyperbaric Medicine: Patient selection, treatment
procedures and side-effects.: Elsevier: New York, 1988:225-235. (Problem
Wounds: The role of oxygen).
The physiological role of adjuvant hyperbaric
Oxygen therapy in trauma management
and rehabilitation
By John Millwood Hargrave
Edited by LIME Research Editor 10 | P a g e