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Hyperbaric Oxygen Therapy in Sports Musculoskeletal Injuries

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Navid Moghadam1, Michinari Hieda2,3, Lindsey Ramey2,3,
Benjamin D Levine2,3, Renie Guilliod2,3
1
Sports Medicine Research Center, Neuroscience Institute, Tehran University of Medical
Sciences, Tehran, Iran; 2Institute for Exercise and Environmental Medicine, Texas Health
Presbyterian Hospital Dallas, Dallas, TX; 3The University of Texas Southwestern
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Medical Center, Dallas, TX

Accepted for Publication: 13 December 2019

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Copyright © 2019 American College of Sports Medicine

Medicine & Science in Sports & Exercise, Publish Ahead of Print
DOI: 10.1249/MSS.0000000000002257

Hyperbaric Oxygen Therapy in Sports Musculoskeletal Injuries

Navid Moghadam1, Michinari Hieda2,3, Lindsey Ramey2,3,

Benjamin D Levine2,3, Renie Guilliod2,3

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1
Sports Medicine Research Center, Neuroscience Institute, Tehran University of Medical

Sciences, Tehran, Iran; 2Institute for Exercise and Environmental Medicine, Texas Health

Presbyterian Hospital Dallas, Dallas, TX; 3The University of Texas Southwestern Medical

Center, Dallas, TX
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Correspondence to:
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Renie Guilliod, MD, Institute for Exercise and Environmental Medicine, 7232 Greenville Ave,

Suite 435, Dallas, TX 75231. Telephone: (214) 345-4619, Fax: (214) 345-4618, E-mail:
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[email protected]
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Conflict of Interest: None. Dr. Hieda was supported by American Heart Association post-

doctoral fellowship grant (18POST33960092) and the Harry S. Moss Heart Trust. The results of

this review are presented clearly, honestly, and without fabrication, falsification, or inappropriate

data manipulation, we also admit that results of the present review do not constitute endorsement

by ACSM.

Copyright © 2019 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
Abstract

Hyperbaric oxygen therapy (HBOT) is a well-established treatment for a variety of

conditions. HBOT is the administration of 100% oxygen breathing in a pressure vessel at higher

than atmospheric pressure (1 atmosphere absolute = 101 kPa). Typically, treatment is given daily

for between one and two hours at pressures of 2.0 to 2.8 ATA, depending on the indication.

Sporting injuries are often treated over 3-10 sessions. HBOT has been documented to be

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effective and is approved in 14 medical indications by the Undersea and Hyperbaric Medical

Society (UHMS), including but not limited to: carbon monoxide poisoning, compromised skin

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grafts and flaps, crush injuries, necrotizing soft tissue infections, and non-healing ulcers with

arterial insufficiencies. Recently, HBOT for sports musculoskeletal injuries is receiving

increased attention. HBOT may allow injured athletes to recover faster than normal rehabilitation
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methods. Any reduction in collegiate and professional athletes’ rehabilitation period can be

financially significant for top-level sports teams; however, further research is required to confirm

HBOT’s benefits on sports musculoskeletal injuries. The purpose of this review to discuss the

current understanding of Hyperbaric oxygen therapy as a treatment modality for common

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musculoskeletal injuries in sport medicine. Moreover, we will highlight the advantages and

disadvantages of this modality as well as relevant clinical and research applications.

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Keywords: Hyperbaric Oxygen Therapy (HBOT), sports musculoskeletal injuries, therapy,

rehabilitation

Copyright © 2019 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
Indications and general protocols of Hyperbaric oxygen therapy (HBOT)

HBOT refers to the administration of pure oxygen intermittently at a pressure higher than 1

atmosphere absolute (ATA) in a hyperbaric chamber. For clinical purposes, the Undersea and

Hyperbaric Medical Society indicates that pressurization should be 1.4 ATA (141.86 kPa) or

higher to be effective. The common range of pressure used is between 2 and 2.8 ATA. (1)

Typically, each session takes between 60 and 120 minutes. Treatment can be carried out in either

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a monoplace or multiplace chamber. The former accommodates a single patient where the entire

chamber is usually pressurized with 100% oxygen, and the patient breathes the ambient chamber

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oxygen directly. The latter holds two or more people (patients, observers, and/or support

personnel) and the chamber is pressurized with compressed air while the patients breathe near

100% oxygen via masks, head hoods, or endotracheal tubes. (1-3) Hyperbaric oxygen therapy
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(HBOT) has been used in a wide variety of medical settings. (4) In the United States, the Food

and Drug Administration (FDA) defers to the Undersea and Hyperbaric Medical Society

(UHMS) to establish the list of indications for which HBOT has sufficient evidence to support its

use. Currently, 14 medical indications have been approved However in other countries a larger
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number of indications are recognized (Table 1). (1) The European Committee for Hyperbaric

Medicine (ECHM) has accepted 30 indications for HBOT. These indications are divided in 3
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categories, ECHM Type 1- 3: Type 1, where HBOT is strongly indicated as a primary treatment

method and its use is supported by sufficiently strong evidence. Type 2, where HBOT is
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suggested and its use is supported by acceptable levels of evidence. Type 3, wehre HBOT can be

considered as a possible/optional measure, but it is not yet supported by sufficiently strong

evidence (5) The branch of Hyperbaric Oxygen Medicine of the Chinese Medical Association

(CMA) endorses 12 emergency indications and 48 non-emergency indications. (6)

Copyright © 2019 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
Potential mechanisms and physiological effects of HBOT

HBOT in the short-term enhances oxygen delivery with vasoconstriction, which reduces

edema; improves neutrophil phagocytic function that mitigates infection; has anti-inflammatory

effects, and mitigates ischemia-reperfusion injury. Over longer time periods and with repeat

administration, HBOT induces neovascularization and neoangiogenesis as well as stimulation of

collagen production by fibroblasts. (7) All of these effects could enhance the rehabilitation of an

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injured muscle in the inflammatory and proliferative phases of recovery.

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The plasma oxygen concentration is normally ~3 ml/L at sea level. (8) Despite the varying need

for oxygenation between different tissues, typical resting tissues need about 60 ml of oxygen/L to

maintain normal metabolism; dissolved oxygen levels can reach this level (60 ml/l plasma),

without considering hemoglobin bound oxygen at a pressure of 3 ATA (304 kPa). (4) During
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carbon monoxide poisoning or in severe anemia without the possibility of transfusion, this

mechanism can help to deliver oxygen without the need for transfer via hemoglobin. Delivering

oxygen at 300 kPa leads to achieving 270 kPa (2,025 mmHg) of oxygen in the arterial blood and
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roughly 53 kPa (~400 mmHg) in the tissues. (4, 9)

The most important effect of HBOT, beyond offering more O2 to the tissues, is producing free
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radicals in a therapeutic range for cell signaling. HBOT induces oxidative stress by mean of

controlled production of reactive oxygen and nitrogen species, which causes the activation of
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cellular processes and pathways. (7, 10-12) Some of the most relevant mechanisms are as follow:

increased growth factors (e.g. hypoxia-inducible factor 1-α [HIF-1α]) (13), vascular endothelial

growth factor (VEGF), (14, 15) stromal-derived factor 1,(13) mobilization of bone marrow-

derived stem cells (CD34), (7) and the reduction of neutrophil adhesion (modification of integrin

β-2) that mitigates ischemia-reperfusion injury. (7, 16)

Copyright © 2019 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
Adverse effects of HBOT

HBOT is mostly safe and the adverse effects are mainly mild and reversible. There are two

main concerns using hyperbaric oxygen therapy, (A) barotrauma (trauma caused by pressure)

and (B) oxygen toxicity (17).

Barotrauma is caused by an inability to balance pressure between the pressurized environment

and any gas-filled space in the body. The middle ear is the most commonly affected place of

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barotrauma, which starts with tympanic membrane hyperemia and can lead to a tympanic

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membrane rupture. Air trapping in sinuses due to obstruction by a polyp or inflammation can

also lead to increased susceptibility to barotrauma. Any air pocket in teeth due to dental decay

can lead to a large amount of pain. An important but rare consideration is barotrauma to the

lungs during depressurization at the end of the HBOT. This represents a risk if the patient holds
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the breath or has a lung condition with air trapping in the airways, which can lead to

pneumomediastinum, pneumothorax or gas embolism.

Oxygen toxicity is a condition resulting from the harmful effects of breathing oxygen at increased
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partial pressures. (18, 19) As noted above, at least some of the beneficial effects of HBOT may

be through controlled oxidative stress. Antioxidant defenses are generally adequate during the
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hyperoxic exposure created by typical clinical hyperbaric oxygen therapy. Nonetheless, there

may be negative aspects to high levels of oxygen radicals and oxygen toxicity in the central
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nervous system can occur. (17) Central nervous system (CNS) oxygen toxicity manifests as

symptoms such as visual changes, ringing in the ears, nausea, twitching, anxiety, confusion, and

dizziness. The CNS oxygen toxicity during clinical hyperbaric oxygen treatment is an oxygen

toxicity seizure. (17) Pulmonary oxygen toxicity (POT) is caused by exposure of the lungs to

oxygen. While described after prolonged normobaric exposures to concentrations above 50%,

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the development of POT manifestations is much more rapid with hyperbaric exposure. POT is

characterized by acute exudative manifestations including edema, hemorrhage and cell

destruction, and subacute proliferative manifestations including fibrosis and hyperplasia.

Clinically important POT is highly unusual in association with routine doses of HBOT, but can

occur with prolonged exposures. (17)

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HBOT for sports musculoskeletal injuries

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HBOT has become popular among injured athletes because of its hypothetical benefits on

accelerated recovery, especially among professional athletes or those with substantial financial

resources. However, despite the widespread popular appeal, the evidence supporting this practice

is meager. Previous reviews have investigated the possible role of HBOT in specific injuries or
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sports injuries in general (2, 3, 20-22) but there has not been any new review since 2005.
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Muscle injury and HBOT

Muscle injuries encompass a broad range of pathologies, including muscle cramps, delayed
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onset muscle soreness (DOMS), muscle contusion and muscle tears (23). Muscle tears (often

referred to as muscle strains) are one of the most common musculoskeletal injuries and can
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account for prolonged time missed from sport. In a recent study of injuries among national

collegiate athletes from 2009- 2015, muscle strains were found to be the second most common

diagnosis that resulted in missed participation for more than 21 days (24). While historically

classified into 3 grades based on severity of symptoms and degree of tear, ranging from small

partial tear to complete rupture, a number of new classification systems have been proposed.

Currently, there is little consensus on a comprehensive and evidenced based system to classify

Copyright © 2019 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
muscle injuries (25). DOMS is characterized by discomfort in skeletal muscles after more than

usual intensity exercise; it peaks in 24-48 hours after the exercise and is typically resolved in 5-7

days. This muscle damage can lead to a transient decline in physical performance (26) and/or

increased risk of injury (27). The ability for sports physicians to reduce the recovery period after

muscle injuries is extremely significant, especially in the realm of financial incentives in

professional sports where slightly faster return to play is of most importance in the light of

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economy of professional sports. The team has to continue paying the salary of injured athlete

despite the fact that he or she is not playing; as an example, the cost of salaries for injured

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players on the disabled list of Major League Baseball was over $1.6 billion dollars in 2013 to

2015.(28) this demand for faster return to service is also the case in military settings. (29)

Few clinical studies have suggested an advantage of HBOT for sports injuries over routine care,
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especially DOMS. (see TABLE 2)

Potential Mechanism of HBOT for muscle injury in acute and proliferative phases
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Acute phase: inflammation after muscle injury includes the production and release of

inflammatory cytokines, increased vascular permeability, migration of neutrophils, and edema.

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(30) Edema increases the diffusion distance for oxygen while at the same time, increases in

extracellular pressure can reduce perfusion, a combination that can result in significant hypoxia
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and necrosis (31) Delivering oxygen by HBOT without an increase in vascular dilation and

permeability can hypothetically simultaneously reduce edema and hypoxia. Under the effect of

HBOTs, the transition from an inflammatory state to a proliferative state is accelerated. This

accelerated transition has been evidenced through the increase in the number of anti-

inflammatory M2 macrophages (M2) in compare to pro-inflammatory M1 Macrophages (M1) in

Copyright © 2019 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
Oyaizu et al study. (32) It has been shown that HBOT accelerates the differentiation of migrated

M1 macrophages to M2 macrophages in the initial phase of healing period (32, 33).

Proliferative phase: Satellite cells play a vital role in the proliferative phase of muscle

rehabilitation after the injury. (34) Satellite cells can undergo transformation to myoblast lineage

to initiate muscle regeneration. (35) Previous studies have shown that HBOT promotes a higher

number of proliferating, differentiating and quiescent satellite cells which will be reserved for the

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next injury (32, 35). One of the important conclusions of Oyaizu and colleagues’s study (32) is

that HBOT accelerated regeneration processes including satellite cell proliferation (resident stem

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cells) with improved muscle fiber regeneration and strength. Chaillou et al. showed that the

myogenic activity of satellite cells can be compromised in the hypoxic environment (34).

Macrophages, neutrophils, and satellite cells in injured muscles release interleukin-6 (IL-6); IL-6
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is involved in the IL-6/STAT3 pathway that increases the expression of the genes needed for the

proliferation of satellite cells and differentiation to myoblast lineages. (32) A study of HBOT in

animal models showed earlier activation of the IL-6/STAT3 pathway compared to their cohorts

in the control group (32). In conclusion, the in vitro studies suggest that HBOT can accelerate the
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needed proliferation and differentiation of proliferative phase.

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Delayed onset muscle soreness

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Staples et al. demonstrated the effects of HBO on the faster recovery of DOMS in athletes

for the first time (36), but several subsequent studies have shown inconsistent results. (21, 37-39)

(see TABLE 2). In their systematic review, Bennett et al demonstrated higher pain scores at 48

and 72 hours in the HBOT group and no differences in longer-term pain, or swelling or muscle

strength at any time.(2) There have been no further published randomized studies since that

review.

Copyright © 2019 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
Webster et al. showed that HBOT led to decreased pain, and increased torque and recovery in

DOMS subjects (40) with a sample size of 12 patients (six HBOT and six control groups).

Mekjavic et al has been the only study which has incorporated completely similar controls with

the intervention group in terms of pressure (2.5 ATA normoxic, PIO2 = 0.2 ATA) (41); the

placebo in other studies was pressurized ambient air with lower pressure than the intervention

group. Using lower fraction oxygen controls to achieve an FiO2 of 0.2 as in Webster et al can be

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controversial due to the increased risk of decompression illness and other concerns about

possible (untested) therapeutic effects of pressure itself or the increased pressure of N2(42), We

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have discussed the concerns about the placebo pressure later in the Performance bias section.

Muscle strain and/or contusion

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We couldn’t find any human clinical studies about using HBOT for athletes with muscle

strain and/or contusion.

Cervaenes et al. showed that HBOT exposed rats had lower creatinine kinase level, a marker of
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muscle damage (43) compared to a control group in a rat model of muscle contusion. They also

measured the weight of the injured muscle 72 hours after injury and showed that the HBOT
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group had higher muscle weight in comparison to the control group. This finding should be

interpreted with caution however since other studies that have used muscle weight as a marker of
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inflammation and have shown lower muscle weight in HBOT groups (32). Best et al. used a

rabbit animal model of tibialis anterior injury in 1998. They showed a significant difference in

isometric torque deficit of injured muscle between the HBOT and control groups. Best et al.

suggested that 5 sessions of HBOT 24 hours after the muscle-tendon unit injury can lead to better

morphologic healing in the HBOT group as well as better isometric torque results. (44) The

number of new in vitro and animal studies and the need for guidance in future studies required us

Copyright © 2019 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
to reevaluate the current literature, search for gaps in the current literature, and offer suggestions

for future studies (45).

Ligament and Tendon injuries

Horn et al. have reported that higher destructive force is needed before reaching failure in

the medial collateral ligament (MCL) of rats treated with HBOT compared with a control group

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after induction of ligament tear and surgery; however, this difference was only apparent 4 weeks

after the injury and they couldn’t find any difference after 6 weeks. (46) Ishii et al. showed a

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dose-response relationship between the concentration and pressure of oxygen in HBOT and its

effect on the healing process of ligament healing in rats. They reported that HBOT at 2 ATA was

the most effective at enhancing collagen synthesis in the extracellular matrix. (47)
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The expression of matrix metalloproteinases (MMPs) and type I procollagen are indicators of the

beginning of the proliferation phase in the process of ligament healing (48). Takeyama et al.

studied using HBOT in the healing of MCLs and anterior cruciate ligaments (ACL) in rats after
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laceration. Both ACLs and MCLs in the HBOT group showed significantly greater gene

expression of type I procollagen and no change in type III procollagen gene expression compared
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to the control group. While MCLs in the HBOT group showed macroscopic healing by scar

tissue formation, none of the severed ACLs united physically despite the administration of
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HBOT. This finding can be attributed to the intra-articular location of the ACL (avascularity) in

contrast to extra-articular of the MCL. MMP gene expression was higher in MCLs in the HBOT

group compared to the MCLs in the control group. The expression of tissue inhibitors of

metalloproteinases (TIMPs) was higher in ACLs in the HBOT group compared to ACLs in the

control group (48). While Takeyama studied the effectiveness of HBOT on ACL lacerations

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without any other intervention, Yeh et al. used HBOT as an adjunct therapy to ACL tendon graft.

They reported increased neovascularization and enhanced incorporation between tendon grafts

and bone in the HBOT group. They also showed that tendon grafts have higher maximal pullout

strength in the HBOT group. (49) Chan et al. designed a 4-arm study to test HBOT and platelet-

derived growth factor-BB’s (PDGF-BB) effect on cultured cells in rabbit MCLs; HBOT and

HBOT plus PDGF-BB groups showed a decrease in Type III collagen/Type I collagen content

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ratio, which can lead to mechanically stronger collagen fibrils. Hsu et al. used HBOT in rabbits

suffering from patellar tendinopathy, which was induced by collagenase; tendons in the HBOT

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group showed 34.8% greater ultimate tensile load compared to the control group. Finally, and

perhaps more concerningly, Mashitori et al. reported a higher amount of scar tissue and Type I

procollagen gene expression in the injured MCL of the rats in a HBOT, compared to the control
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group. (50) Only two randomized, controlled, human trials using HBOT in ligament injuries

(MCL and ankle sprain) have been reported to date. Both were small, had methodological

problems and were inconclusive. (51, 52) Basic and animal studies have justified moving on and

designing human studies to investigate the clinical effectiveness of using HBOT in ligament and
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tendon injured athletes.

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Limitations of current human studies:

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Selection Bias

We cannot reject the possibility of baseline differences between groups, especially

when the subjects are recruited after injury and the investigator has no prior data. Soolsma et al.

(HBOT for MCL injury) did not report the baseline data after the outcome measures in the

groups. (51) Borromeo et al. (HBOT for ankle sprain) did report baseline measurement and

Copyright © 2019 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
there were significant differences between the groups regarding initial pain and edema (worse in

HBOT group); however, the time from injury to first HBOT, and the range of motion and ankle

function (main outcome) were uniform. (52) Among DOMS studies, Staples et al. did not report

any statistical test for investigating baseline differences between groups, they just have shown

the baseline date in the raw data manner in figures; it should be mentioned that HBOT groups

had higher baseline eccentric torque forces than other groups according to the reported figures in

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their study. (36) Mekjavic et al. also did not conduct baseline measurements in HBOT and

control groups. (41) Harrison et al. reported no difference between HBOT and control groups in

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isometric strength but did not report any test for evaluation of baseline cross-sectional area, T2

relaxation time and serum creatinine kinase. (39) Webster et al. did not report baseline values

and only reported outcomes as percentage change from non-disclosed baselines, except for the
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cross-sectional area, which they did reported baselines for and emphasized no significant

differences between groups. It is important to mention that Webster et al. is the only study that

could reproduce the findings of Staples et al. about HBOT’s effectiveness in treating DOMS.

(40) Babul et al. reported a 95% confidence interval of zero mean difference between control and
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HBOT groups and included all baseline measurements. (38) Germain et al. reported baseline

values in figures and tables without mentioning any statistical test for checking baseline
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difference between groups. (37) We have to emphasize the importance of reporting baseline

characteristics of intervention and control groups in future studies. We can use less intimidating
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tests like isometric muscle strength testing, which can be conducted even with injured athletes.

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Performance bias

The only human trial which used the same pressure in the chamber for both HBOT and

control groups was Mekjavic et al. (41); Soolsma (51), Borromeo et al. (52), Staples et al. (36),

Webster et al. (40) and Babul et al. (38) used 1.1, 1.2 or 1.3 ATA of pressure as sham. There are

some concerns that this last type of sham is less effective in blinding than a controls intervention

with the same pressure with HBOT but with hypoxic mixture to mimic normoxic conditions

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(PIO2 = 0.2 ATA). However Weaver et al ran a prospective study to test if the divers or other

people familiar with hyperbaric situation can discern chamber pressure (1.5 ATA 100% oxygen

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vs. 1.2 ATA ambient air). They showed that experienced divers could not discriminate chamber

pressures of 1.5 ATA and 1.2 ATA. (53) but they did not reach 2.0 or 2.5 ATA which are the

most common protocols. Clarke reported that recreational SCUBA divers could not differentiate
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between 2.0 ATA 100% Oxygen and 1.1-1.3 ATA ambient air protocols. (54) However, it did

not report in detail how they evaluated the effect of learning on repeated exposures. A narrative

review by Lansdrop and van Hulst in 2018 concluded that the best placebo is using air with a

lower pressure than the hyperbaric oxygen therapy group. (55) In the authors’ opinion however,
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there are still two theoretical concerns with this approach:

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1. It is not possible to simultaneously treat subjects of the study group with subjects of the

control group, nor is possible to have patients under treatment pressure and study subjects
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of the control group at the same time; (which means they cannot be treated exactly the

same). With the placebo approach using the same treatment pressure (2 ATA, for

example) breathing a hypoxic mixture (10.5% oxygen and 89.5% nitrogen), patients and

study subjects of both groups (control and study) can be treated in the chamber at the

same time, completely blinded.

Copyright © 2019 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
 2. In the vast majority of multiplace hyperbaric chambers, it is not possible to obtain an

appropriate door seal until the internal pressure reaches at least 1.2 ATA. Without

enough pressure to obtain the proper seal, a characteristic noise is produced that would

inform the study subjects, and the personnel inside and outside the chamber, that there is

little pressure inside the chamber. .

We should also mention that control groups did not receive any treatment in Harrison et al. (39)

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and Germain et al. (37) studies.

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Detection bias

Half of the eight human trials have used blinded assessor for the outcome measurements
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(TABLE), three of eight studies did not mention if the assessors of the outcomes measure were

blinded and Webster et al. specified that their study was single blinded. (40)
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Future strategies to bridge the knowledge gap

We suggest that future studies use larger sample sizes or matching to avoid differences in
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the baseline of HBOT and control groups. They could report baseline data if there is no

difference in the baseline measures of outcome measures. Blindness strategy is another concern
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in future study designs, and the aforementioned concerns about the blindness should be

addressed. The blindness of the investigator who is responsible for the assessment of outcome

measures can attenuate substantial bias.

All the current human trials have mentioned randomization in their design, but

considering the limited number of participants, randomization might not be enough for

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attenuating allocation bias. We suggest that future studies use large pools of injured athletes with

different injuries but with stratification and matching. They can use relative outcomes (healing

time of any specific injury in HBOT group/healing time of the same injury in control group) as

an outcome measure, which enables them to use a pool of injured athletes with different injuries.

Despite the number of basic and animal studies using HBOT in conditions other than muscle

soreness, human trial studies are scarce. Designing new human studies for evaluation of the

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effectiveness of HBOT on muscle strains, contusion, tendon and ligament injuries should be the

next step in the light of recent in vitro and animal studies.

Conclusion

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Hyperbaric Oxygen Therapy (HBOT) has the special capacity to enhance oxygen delivery,
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reduce edema and pathologic inflammation, mitigate ischemia/reperfusion injury, improve

collagen synthesis and deposition, and induce neovascularization and neoangiogenesis. These

underlying mechanisms have the potential to help the process of healing among injured athletes.
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The last meta-analysis and systematic review still stands which had suggested that HBOT is

ineffective for Delayed muscle soreness. The human studies are scarce despite widespread use of
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HBOT among athletes and require rigorous scientific studies before concluding if HBOT can

facilitate the return to play of athletes.

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Conflict of interest

None.

Funding

Dr. Hieda was supported by American Heart Association post-doctoral fellowship grant

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(18POST33960092) and the Harry S. Moss Heart Trust.

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Acknowledgment

The results of this review are presented clearly, honestly, and without fabrication,
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falsification, or inappropriate data manipulation, we also admit that results of the present review

do not constitute endorsement by ACSM. We would like to thank you, Jason Kawalsky, for your

revision in English.
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 Table 1. Therapeutic uses of hyperbaric oxygen according to Undersea and
Hyperbaric Medical Society (UHMS)
1. Air or gas embolism
2. Carbon monoxide poisoning / Carbon monoxide poisoning complicated by
cyanide
poisoning
3. Clostridial myositis and myonecrosis (gas gangrene)
4. Crush injuries, compartment syndrome and other traumatic ischemias
5. Decompression sickness
6. Arterial Insufficiencies

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a. Central retinal artery occlusions
b. Selected problem wounds - diabetic ulcers (microvascular
insufficiency)
7. Severe anemia

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8. Intracranial abscesses
9. Necrotizing infections
10. Osteomyelitis (refractory)
11. Delayed radiation injury (soft tissue and bony necrosis)
12. Compromised grafts and flaps
13. Acute thermal burn injury
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14. Idiopathic sudden sensorineural hearing loss

The Undersea and Hyperbaric Medical Society approves use of hyperbaric

oxygen for a few conditions for which there is thought to be reasonable
scientific evidence or well validated clinical experience.(2)
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Table 2. Summary of human clinical trials for HBOT in sports related injuries
Summary of Results (effect of HBOT in compare to the
Reference Injury type groups Intervention
control)

10 sessions ↓volume of edema

HBOT group
of 2.5 ATA ↓muscle wasting
N=7
100% O2 ↑range of motion

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Soolsma, grade II medial collateral
↑Maximum flexion
1996 (48) ligament injury
Control 10 sessions
↔ Severity of pain
Group of 1.2 ATA
↔ One legged jump test

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N=7 air

3 sessions 2 ↑functional index improvement *

HBOT group
Borromeo ATA 100%
N=16 ↔ reduced swelling
et al., Ankle sprain within 72 hr O2
↔ pain
1997 (49) control group 3 sessions ↔ range of motion

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N=16 1.1 ATA air ↔ time to recovery
Phase 1 Phase 1
3 sessions ↔ Pain score
2.5 ATA ↑Recovery of torque (HBO vs. Delayed HBO, Sham, and
100% O2 and control) *
HBO group
2 sessions
N=9
1.2 ATA
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21% O2 after
Staples et that
Induced DOMS of
al., 2 sessions
quadriceps
1999(33) 1.2 ATA
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Delayed 21% O2 and
HBO group 3 sessions
N=9 2.5 ATA
A

100% O2
after that
Sham group 5 sessions Phase 2
N=9 1.2 ATA ↔ Pain score

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 21% O2 ↑Mean eccentric quadriceps torque (5 days HBO vs. Sham
Control and 3 days HBO) *
group No treatment
N=9
Phase 2
3 days HBO 3 sessions
group 2.5 ATA

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N=10 100% O2
5 days 5 sessions
HBO group 2.5 ATA
N=10 100% O2

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5 sessions
Sham group
1.2 ATA
N=10
21% O2
7 sessions
HBOT 2.5 ATA
groups 100% O2
↔ the rate of recovery

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N=12 (PIO2 = 2.5
Mekjavic
Induced DOMS of elbow ATA) ↔ muscle strength
et al.,
flexors 7 sessions ↔ peaked Perceived soreness
2000 (38)
control 2.5 ATA ↔ increases in arm circumference
groups normoxic
N=12 (PIO2 = 0.2
ATA)
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5 sessions
Immediate 2.5 ATA
HBOT 100% O2
N= 6 (starting day ↔ cross-sectional area
Harrison
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exercise-induced muscle 0) ↔ T2 relaxation time in MRI
et al.,
injury with Preacher Curl 4 sessions ↔ isometric strength serum CK level
2001 (36)
Delayed 2.5 ATA ↔ perceived soreness
HBOT 100% O2
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N=7 (starting day

1)

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 control group
no treatment
N=7

↑isometric peak torque recovery *

3 sessions of
HBOT group ↓pain perception *
2.5ATA
Webster et N=6
exercise-induced muscle 100% O2
al., 2002 ↔ isokinetic peak torque

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injury in gastrocnemius
(37) ↔ muscular endurance
3 sessions of ↔ T2 relaxation time in MRI
control group
1.3 ATA air ↔ cross-sectional area
N=6

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5 sessions of ↔ Pain
HBOT group
2.0ATA ↔ Strength
Babul et N=8
Induced DOMS of knee 100% O2 ↔ quadriceps circumference
al., 2003
flexors ↔ creatine kinase
(35) control group 5 sessions of
↔ malondialdehyde
N=8 1.2 ATA air
↔ MRI images (T2 and STIR)

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HBOT group 5 sessions of
Germain N=8 2.5ATA 95% ↔ creatine kinase
Induced DOMS of O2 ↔ muscle soreness
et al.,
quadriceps femoris ↔ leg circumference
2003 (34) control group
no treatment ↔ isokinetic peak torque
N=8

* statistically significant (<0.05 P-value) difference between HBOT and control group in that outcome
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Abbreviations: HBOT, Hyperbaric Oxygen Therapy. DOMS, Delayed onset muscle soreness. ATA, atmospheres absolute
↑ shows the outcome variable is higher in HBOT group in compare to control group
↓ shows the outcome variable is lower in HBOT group in compare to control group
↔ shows the outcome variable is similar in HBOT and control group
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