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1986;68:1218-1224. J Bone Joint Surg Am.MJ Skyhar, AR Hargens, MB Strauss, DH Gershuni, GB Hart and WH Akeson    

compartment syndromes associated with hemorrhagic hypotensionHyperbaric oxygen reduces edema and necrosis of skeletal muscle in

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www.jbjs.org20 Pickering Street, Needham, MA 02492-3157The Journal of Bone and Joint Surgery

Copyright 966 by The Journal ol Bone and Jou:t Surgery. Incorporated

1218 THE JOURNAL OF BONE AND JOINT SURGERY

Hyperbaric Oxygen Reduces Edema and Necrosis of Skeletal

Muscle in Compartment Syndromes Associated

with Hemorrhagic Hypotension*

BY M. J. SKYHAR, M.D.t, A. R. HARGENS, PH.D.t, SAN DIEGO, M. B. STRAUSS, M.D4, LONG BEACH, D. H.

GERSHUNI, M.D.t, SAN DIEGO, G. B. HART, M.D4, LONG BEACH, AND W. H. AKESON, MD.I’, SAN DIEGO, CALIFORNIA

From the Division of Orthopaedics and Rehabilitation. Veterans Administration and University of Cal(ftirnia Medical Centers, San Diego.

and the Baromedical Department. Memorial Hospital Medical Center ofLong Beach, Long Beach

ABSTRACT: This study examined the effect of ex-

posures to hyperbaric oxygen on the development of the

edema and necrosis of muscle that are associated with

compartment syndromes that are complicated by hem-

orrhagic hypotension . A compartment syndrome

(twenty millimeters of mercury for six hours) was in-

duced by infusion of autologous plasma in the antero-

lateral compartment of the left hind limb of seven

anesthetized dogs while the mean arterial blood pressure

was maintained at sixty-five millimeters of mercury after

30 per cent loss of blood volume. These dogs were treated

with hyperbaric oxygen (two atmospheres of pure oxy-

gen) and were compared with six dogs that had an iden-

tical compartment syndrome and hypotensive condition

but were not exposed to hyperbaric oxygen Forty-eight

hours later, edema was quantified by measuring the

weights of the muscles (the pressurized muscle compared

with the contralateral muscle), and necrosis of muscle

was evaluated by measuring the uptake of technetium-

99m stannous pyrophosphate. The ratio for edema was

significantly (p = 0.01) greater in dogs that had not been

exposed to hyperbaric oxygen (1 . 15 ± 0.01) than in the

dogs that had been treated with hyperbaric oxygen (1.01

± 0.03), and the ratio for necrosis of muscle was also

significantly (p = 0.04) greater in dogs that had not had

hyperbaric oxygen (1 .96 ± 041) than in those that had

been treated with hyperbaric oxygen (1.05 ± 0.11).

Comparisons were also made with the muscles of four

normal control dogs and separately with the muscles of

six normotensive dogs that had an identical compart-

‘ment syndrome and normal blood pressure and were not

treated with hyperbaric oxygen. The water content and

absolute uptake of technetium-99m stannous pyrophos-

* No benefits in any form have been received or will be received from

a commercial party related directly or indirectly to the subject of this article.Funds were received in total or partial support of the research or clinicalstudy presented in this article. The funding sources were Veterans Admin-istration and National Institutes of Health Grants GM-24901 . AM-26344,

and RCDA AM 00602 to Dr. Hargens.1� Division of Orthopaedics and Rehabilitation (V- I S 1 ). Veterans

Administration and University of California Medical Centers, San Diego.California 92161.

� Baromedical Department. Memorial Hospital Medical Center ofLong Beach, Long Beach, California 90801.

phate in the contralateral control muscles of the four

groups ofdogs were not significantly different, indicating

that the treatment with hyperbaric oxygen primarily

reduced the edema and necrosis that are associated with

compartment syndromes combined with hemorrhagic

hypotension.

CLINICAL RELEVANCE: The results of this study sug-

gest that hyperbaric oxygen may be helpful in treating

patients who have borderline compartment syndrome

(twenty to fifty millimeters of mercury and no neuro-

logical deficit) that is associated with hemorrhagic hy-

potension but that such treatment should be considered

only as an adjunct to the standard treatment of fluid

replacement and fasciotomy. We are now evaluating the

efficacy and indications for hyperbaric oxygen in the

treatment of borderline compartment syndrome in hu-

mans.

Compartment syndrome of skeletal muscle develops

when the intracompartmental pressure is elevated suffi-

ciently to reduce capillary perfusion to the extent that the

intracompartmental tissues become ischemic , non-func-

tional, and necrotic9. We employ a threshold pressure of

thirty millimeters of mercury as one indication for surgical

decompression of a compartment syndrome in the normo-

tensive patient’6. Factors that lower the threshold pressure

for development of compartment syndromes include local

injury to blood vessels, coagulopathy, and systemic

hypotension23. For a model canine hind-limb compartment

syndrome with hemorrhagic hypotension, an intracompart-

mental pressure of twenty millimeters of mercury for six

hours produces a degree of necrosis as great as that produced

by an intracompartmental pressure of forty to fifty milli-

meters of mercury for eight hours in a normotensive dog23.

Trauma to skeletal muscle sometimes leads to an acute

compartment syndrome’6, and severe blood loss also occurs

frequently in patients who have multiple injuries. The hem-

orrhagic shock causes peripheral vascular insufficiency’3,

decreased blood pressure, and reduced blood flow to skeletal

muscle78. Metabolic and respiratory alterations also accom-

pany hemorrhagic shock. These alterations produce resis-

tance to insulin and abnormalities of the metabolism of

HYPERBARIC OXYGEN REDUCES EDEMA AND NECROSIS OF SKELETAL MUSCLE 1219

VOL. 68-A, NO. 8. OCTOBER 1986

amino acid and glucose in skeletal muscle2’9. A study in-

volving injection of xenon- 133 and iodine- 13 1 into skeletal

muscle showed that the transport of nutritive substances and

metabolic products through the interstitial space is impaired

in the presence of hemorrhagic hypotension’4. These

changes lower the threshold pressure for the development

of compartment syndrome23.

Once a compartment has been decompressed, perfusion

is usually improved, but fasciotomy may not be all that is

required to restore function to marginally viable tissues be-

cause edema and ischemia of the tissue do not always resolve

immediately, particularly in the presence of hypotension.

Better and more effective methods for the treatment of com-

partment syndromes are needed.

Strauss et al. determined that intermittent treatment

with hyperbaric oxygen reduced the edema and necrosis of

skeletal muscle significantly in experimentally induced com-

partment syndromes in normotensive animals. The reduction

of edema and necrosis was reflected by ratios of the weight

of muscle and of the uptake of technetium-99m pyrophos-

phate in experimental and control limbs, comparing treated

and untreated dogs. Histological criteria were also used in

grading necrosis of muscle. Histological evidence of ne-

crosis of muscle was reduced in the experimental limbs of

the dogs that received hyperbaric oxygen as compared with

those of the dogs that had an identical compartment syn-

drome but were not treated with hyperbaric oxygen2’.

The purpose of this study was to determine if similar

beneficial effects could be achieved using intermittent

administration of hyperbaric oxygen to treat experimentally

induced compartment syndromes in the hind limbs of dogs

that had hemorrhagic hypotension.

Materials and Methods

Preparation of the Animals

Twenty-three conditioned mongrel dogs weighing sev-

enteen to thirty kilograms were divided into four groups

(Table I). Group 1 consisted of four normal dogs that had

normal blood pressure and in which a compartment syn-

drome was not produced. Group 2 consisted of six dogs that

also had normal blood pressure, but in each of them an

anterolateral compartment syndrome (twenty millimeters of

mercury for six hours) was produced. Group 3 consisted of

six hypotensive dogs that had a compartment syndrome that

was identical to the one produced in the dogs in Group 2.

Group 4 consisted of seven hypotensive dogs that had the

same compartment syndrome as that produced in Groups 2

and 3, and these dogs were treated with hyperbaric oxygen.

One week before production of the compartment syn-

drome in Groups 2, 3, and 4, 250 milliliters of blood was

withdrawn from thejugular vein. The blood was centrifuged

and the plasma was decanted. The red blood cells were

diluted with an appropriate volume of 0.9 per cent sodium

chloride solution and then were returned to the animal. One

day before production of the compartment syndrome, the

dogs were denied food but water intake was not restricted.

Xylazine hydrochloride (one milligram per kilogram of body

weight) was administered intramuscularly as a pre-anes-

thetic agent, followed by intravenous pentobarbital sodium

(twenty milligrams per kilogram ofbody weight). Once they

were anesthetized, the dogs were intubated and connected

to a Harvard respirator. Bicillin (penicillin G benzathine)

(1.2 million units) was administered intramuscularly and

Ancef (cefazolin sodium) (one gram), injected into one liter

of lactated Ringer solution, was infused through the right

brachial vein at a rate of two milliliters per minute during

the compartment syndrome. The right brachial artery was

cannulated for continuous monitoring of the mean central

arterial blood pressure, using a strain-gauge pressure-trans-

ducer and four-channel strip-chart recorder (Hewlett-Pack-

ard). In the dogs that were to undergo hemorrhagic

hypotension (Groups 3 and 4), the left jugular vein was

cannulated with K-SO tubing and was ligated distally. The

tubing was tunneled subcutaneously to an exit incision dor-

sally on the dog’s neck and then was anchored with sutures

to serve as permanent access to the central venous system.

The patency of this central venous line was maintained by

intermittent flushing with heparinized saline. The left carotid

artery was cannulated with silicone-treated PE-240 tubing

(Clay Adams) and was ligated distally for the initiation of

hemorrhage. Heparmn (5,000 units) was given intravenously

at the time of cannulation, with hourly supplements of 500

units during the hypotensive period. The dog’s core tem-

perature was maintained at 38 degrees Celsius by a heating

pad placed beneath the animal, and the temperature of the

gastrocnemius muscle was maintained at 34 degrees Celsius

using an infrared lamp. Both temperatures were monitored

continuously with probes and a thermistor thermometer

(Rochester Electro-Medical, model B-2).

Hemorrhagic Shock

Shock was induced by a slow hemorrhage in the dogs

in Groups 3 and 4 (Table I); approximately 30 per cent of

the calculated blood volume was allowed to flow from the

cannulated left carotid artery into a reservoir over a period

of twenty minutes. The mean arterial blood pressure was

monitored and the hemorrhage was continued, if necessary,

until an arterial pressure of sixty-five millimeters of mercury

was obtained. The average volume of blood that was with-

drawn was fifty-six milliliters per kilogram of body weight.

The arterial pressure was maintained by adjusting the res-

ervoir to an appropriate height above the level of the heart

So that the open catheter and tubing produced a hydrostatic

column of blood that maintained the animal’s arterial pres-

sure constant at sixty-five millimeters of mercury. Further

adjustments in height usually were not necessary. After six

hours of compartment syndrome under hypotensive blood-

pressure conditions, the blood was warmed to 38 degrees

Celsius and returned to the animal.

Model Compartment Syndrome

Autologous plasma was warmed to 37 degrees Celsius,

filtered, and infused intramuscularly into the anterolateral

muscle compartment of the left hind limb through a 19-

1220 M. J. SKYHAR ET AL.

THE JOURNAL OF BONE AND JOINT SURGERY

TABLE I

AMPLITUDE AND D URATION OF INTR ACOMPARTMENTAL PRESSURE IN TH E EXPERIMENTAL HIND LIMBS

Mean Arterial Blood

No. of Pressure during

Group Dogs Compartment Syndrome

(mm Hg)

Amplitude Duration

(mm Hg) (Hrs.)

Groupl: 4 95±5 0 0

normal controls (no compartment syndrome)

Group2: 6 98±6 20 6

no hyperbaric

oxygen, normal

blood pressure

Group 3: 6 65 20 6

no hyperbaric

oxygen. reduced

blood pressure

Group 4: 7 65 20 6

hyperbaric

oxygen, reduced

blood pressure

gauge needle. The rate and volume (approximately seven

to nine milliliters) of plasma that was injected was sufficient

to elevate intracompartmental pressure to twenty millimeters

of mercury in Groups 2, 3, and 4 (Table I). This pressure

was maintained for six hours by adjusting the height of the

reservoir of autologous plasma above the site of the infusion.

In the dogs in Group 1 , an infusion needle was placed in

the left anterolateral compartment but no plasma was in-

fused. Intramuscular pressures were monitored continuously

by strain-gauge transducers at proximal and distal sites in

the left anterolateral compartment of each dog using slit

catheters”, and the pressures were recorded on a strip-chart

recorder. In each animal, the left anterolateral compartment

was pressurized and the contralateral compartment served

as the control. An infusion needle and slit catheters were

placed in an identical fashion into the control leg to nor-

malize their effects on the formation of edema and uptake

of technetium-99m stannous pyrophosphate in each leg.

Protocols for Animals in Groups 3 and 4

For dogs in Groups 3 and 4 (Table I), at the completion

of six hours of hemorrhagic shock with pressurization of

the left anterolateral compartment (twenty millimeters of

mercury for six hours), normal blood pressure was restored

by transfusion with autologous whole blood. If necessary,

saline solution was also infused to restore the normal base-

line blood pressure. Each dog was allowed to recover par-

tially from the anesthesia so that intubation and the Harvard

respirator were no longer necessary . The intracompartmen-

tal catheters, carotid and brachial artery catheters, and tem-

perature probes were removed, but the jugular-vein infusion

site was maintained with a heparin lock. The dogs were

taken to the vivarian recovery room, where they were mon-

itored until they were fully awake. They were given one to

two milligrams per kilogram of body weight of meperidine

intramuscularly for analgesia.

During the twelve hours after the six-hour episode of

compartment syndrome, the dogs in Group 3 were confined

to a recovery cage, where they usually slept. Forty-eight

hours after onset of the compartment syndrome , the amounts

of necrosis of muscle and edema were determined for Group

3 exactly as will be described for the dogs in Groups 1 , 2,

and 4.

Within fifteen minutes after removal of the intracom-

partmental catheters, each dog in Group 4 was put in a

monoplace hyperbaric chamber (Vickers clinical hyperbaric

oxygen system, CHS/3) for a one-hour exposure to pure

oxygen at two atmospheres of absolute pressure while the

animal breathed spontaneously. Access to the jugular-vein

catheter from outside the chamber was established by con-

necting the tubing to an intravenous-line port in the bulkhead

of the chamber. The line was occasionally flushed with

heparinized normal saline solution. The dog was kept lightly

sedated with intravenous pentobarbital sodium (ten milli-

grams per kilogram of body weight) as necessary during

treatment with hyperbaric oxygen. After the first one-hour

exposure to hyperbaric oxygen, the dog was returned to its

cage. Four hours later, a second one-hour treatment with

hyperbaric oxygen was administered, and after four more

hours a third treatment was given, so that each dog had

three one-hour exposures to hyperbaric oxygen over an

eleven-hour period. The amounts of swelling and tenseness

of the experimental and control anterolateral compartments

were observed and compared before and after each exposure

to hyperbaric oxygen.

Quantification of Necrosis of Muscle and Edema

Intracompartmental skeletal necrosis of muscle was

quantified by uptake of technetium-99m stannous pyro-

phosphate, as described by Hargens et ‘ ‘ . Forty-eight

hours after the onset of pressurization of the compartment,

each animal was sedated by an intramuscular injection of

xylazine (fifty milligrams). A bolus of five millicuries of

technetium-99m pyrophosphate was then injected intrave-

nously into the brachial vein. The dog remained sedated

and was held upright by a cloth sling under the abdomen

GROUP 3

120

100

80

I

GROUP 4

60

:t:EE

I

I I

80 \�

-1 0 1 2 3 4 5

TIME (hrs)

FIG. 1

0 1 2 3 4 5 6

TIME (hrs)

VOL. 68-A, NO. 8. OCTOBER 1986

HYPERBARIC OXYGEN REDUCES EDEMA AND NECROSIS OF SKELETAL MUSCLE 1221

to equalize circulation of the blood in the two hind limbs.

Three hours after injection of the isotope, the dog was killed

with an overdose of intravenous pentobarbital sodium. The

three major muscles of the anterolateral compartment (tib-

ialis cranialis, extensor digitorum longus, and fibularis lon-

gus) were removed from both limbs simultaneously by two

operating teams.

The three muscles comprising the muscle groups from

each side were weighed individually for the evaluation of

edema, as previously described2’ . An index for edema was

calculated as the ratio of the weight of muscle on the ex-

perimental side to that on the control side. Experimental

and control muscle groups from each animal were cut into

one-centimeter-thick segments for studies of radioactivity.

Each segment that was obtained in this fashion was weighed,

and its uptake of technetium-99m stannous pyrophosphate

was determined in a gamma well-counter (Chicago Nuclear,

model 1 185). Triplicate standard samples, each diluted iO�

times from the original injection solution of technetium-

99m pyrophosphate, were used to determine the absolute

uptake and to permit comparison between the different dogs.

Each segment was counted for gamma radioactivity, and

the data for all segments of muscle and standard samples

were corrected for decay of radioactivity. The percentage

of the total dose of technetium-99m pyrophosphate in each

sample was then calculated. Ratios of the uptake in the

experimental limb to that in the control limb were deter-

mined using the sum of the uptake of isotope in the segments

from the pressurized muscles and the sum of the uptake in

the segments from the contralateral control muscles of each

dog.

Two other groups of dogs (Groups 1 and 2) were in-

cluded to rule out the possible systemic effects of hemor-

rhagic hypotension or hyperbaric oxygen, or both, on

absolute uptake of technetium-99m pyrophosphate in the

contralateral control muscles. The ratios of uptake for the

dogs that were treated with hyperbaric oxygen (Group 4)

were then compared with the ratios for the six dogs that

were treated in an identical manner but were not exposed

to hyperbaric oxygen (Group 3). The results for uptake of

technetium-99m pyrophosphate from our previous study,

done without hyperbaric oxygen23, were included for pur-

poses of comparison with animals that were treated with

hyperbaric oxygen in the present study. Using paired and

(I)

� 100

(I)

w

ci�

wI-

w

U-0

uJ

Condensed plots of the maximum range of mean arterial pressure (indicated by bars above and below the median) for four representative dogs inGroup 3 and four representative dogs in Group 4. The mean arterial pressures are presented for the hour preceding hemorrhage and for each hourduring the period of hemorrhagic hypotension. During the hypotensive period. the arterial pressures of some dogs changed abruptly from sixty-fivemillimeters of mercury, but immediate adjustments were made to restabilize the pressure at sixty-five millimeters of mercury. The data points that aremarked with an asterisk indicate essentially no variation of mean arterial pressure for the given hour.

60

1222 M. J. SKYHAR El AL.

1.50

��10

I-

� 1.00C.)

-I

Li

LU .><Lii

I�4A��GROUP I GROUP 2 GROUP 3 GROUP 4

FIG. 2

Comparison of weights of the muscles of the anterolateral compartment of the normal dogs and of the three groups of dogs with compartmentsyndrome. Group 1 consisted of normal controls; Group 2, dogs that had compartment syndrome, normal blood pressure, and no treatment withhyperbaric oxygen; Group 3, dogs that had compartment syndrome, hypotension, and no treatment with hyperbaric oxygen; and Group 4, dogs thathad compartment syndrome, hypotension, and treatment with hyperbaric oxygen. The results (mean and standard error) are expressed as ratios of theweight of the experimental anterolateral compartment to that of the contralateral anterolateral compartment. The Group-4 dogs had significantly lessedema than did the Group-3 dogs (p = 0.01). Two days after pressurization, the Group-2 dogs did not have significant edema as compared with theGroup- I dogs. The water content of the contralateral compartment was not different in the four groups of animals.

-J

0

0

GROUP I GROUP 2 GROUP 3 GROUP 4

FIG. 3

Comparison of ratios of uptake of technetium-99m stannous pyrophosphate of the muscles of the anterolateral compartment of the normal dogs andof the three groups of dogs that had compartment syndrome. Group 1 consisted of normal controls; Group 2, dogs that had compartment syndrome,normal blood pressure, and no treatment with hyperbaric oxygen; Group 3, dogs that had compartment syndrome, hypotension, and no treatment withhyperbaric oxygen; and Group 4, dogs that had compartment syndrome, hypotension, and treatment with hyperbaric oxygen. The results (mean andstandard error) are expressed as ratios of the uptake in the experimental anterolateral compartment to that in the contralateral anterolateral compartment.Group-4 dogs had significantly less necrosis of muscle (uptake of pyrophosphate in the experimental leg) than did Group-3 dogs (p = 0.04). Forpurposes of comparison, results for uptake from a previous study of hypotensive dogs that had an identical compartment syndrome and were not treatedwith hyperbaric oxygen23 are included in this figure only. The Group-2 dogs did not have significant necrosis as compared with the Group-i dogs. Theuptake of pyrophosphate in the contralateral compartment was not different in the four groups of animals.

unpaired Student t tests, the statistical significance was set in four representative animals from Groups 3 and 4 during

at p < 0.05. the experimental period demonstrated that the blood pres-

sures of these hypotensive dogs were maintained at essen-

Results tially the same levels during the six-hour compartment

Plots of the mean and range of arterial blood pressures syndrome (Fig. 1). After this period, the intracompartmental

ThE JOURNAL OF BONE AND JOINT SURGERY

0

I-:�:

w

I-

w

I-

0()

-JC-)(I):D

0I-

L�J

0�

:i:0�

0:i:0�0

>-

0�

HYPERBARIC OXYGEN REDUCES EDEMA AND NECROSIS OF SKELETAL MUSCLE 1223

VOL. 68-A, NO. 8. OCTOBER 1986

catheters were removed and the blood pressure of the ani-

mals was restored to normal. Group-4 animals were then

treated with hyperbaric oxygen and Group-3 animals were

not.

Qualitatively, there was reduction of tenseness and

swelling in the experimental compartments of the dogs that

were exposed to intermittent hyperbaric oxygen. All dogs

in Groups 3 and 4 recovered uneventfully from the hypo-

tensive period. All dogs were killed two days after the

episode of compartment syndrome (sham compartment syn-

drome for Group 1).

The effect of hyperbaric oxygen on edema of muscle

is reflected by the muscle-weight ratios of the experimental

and contralateral control limbs (Fig. 2). The mean ratio for

the dogs that were treated with hyperbaric oxygen (Group

4) was unity and was significantly less (p = 0.01) than the

ratio of 1 . 15 for the dogs that were not exposed to hyperbaric

oxygen (Group 3). Necrosis of muscle, as quantified by

uptake of technetium-99m pyrophosphate, was significantly

reduced (p = 0.04) in Group-4 dogs as compared with

Group-3 dogs (Fig. 3). Accumulation ofthis radionucleotide

indicates irreversible ischemic injury, since pyrophosphate

is absorbed by the calcium deposits of necrotic and severely

injured cells’ ‘ . The mean ratio for the dogs that were not

exposed to hyperbaric oxygen was 1 .96, indicating in-

creased uptake of technetium-99m pyrophosphate and ver-

ifying necrosis in the experimental limb. However, the mean

ratio for the dogs that were treated with hyperbaric oxygen

was 1 .05, reflecting significantly less damage to muscle in

the experimental limb.

As compared with normal control dogs (Group I ), ra-

tios of uptake of technetium-99m pyrophosphate for dogs

in Group 4 (compartment syndrome with hypotension and

treatment with hyperbaric oxygen) and Group 2 (compart-

ment syndrome with normal blood pressure and no treatment

with hyperbaric oxygen) were not significantly different

(p = 1 .00 and p = 0.66, respectively). These results in-

dicate that the experimental muscles of the dogs in Groups

1 , 2, and 4 were essentially normal, with uptake of tech-

netium-99m pyrophosphate about equal to that in the con-

tralateral muscles. Also, the absolute water content and

absolute uptake of technetium-99m pyrophosphate per gram

of tissue were not different in the contralateral control mus-

des of the four groups of dogs in this study (minimum p

= 0.68). This is important because our comparisons of

ratios for the experimental and control sides for weight and

uptake of pyrophosphate assumed that the contralateral (con-

trol) muscle remains normal in terms of water content and

uptake of pyrophosphate despite exposure of the animal to

hemorrhagic hypotension or hyperbaric oxygen, or both.

Discussion

As has been previously demonstrated in the normoten-

sive state2’ , in the hypotensive state hyperbaric oxygen also

significantly reduces edema and necrosis of muscle after an

induced compartment syndrome. This is reflected by re-

ductions in the edema and necrosis of muscle in the dogs

that were treated with hyperbaric oxygen compared with the

dogs that were not treated with hyperbaric oxygen. The

mechanisms by which hyperbaric oxygen reduces necrosis

of skeletal muscle in compartment syndromes associated

with hemorrhagic hypotension are probably similar to those

elucidated by Strauss et al. for the normotensive state:

namely, hyperoxygenation and vasoconstriction.

Hyperoxygenation increases the amount of physically

dissolved oxygen in the fluids of plasma and tissue and is

directly proportional to the partial pressure of inhaled

oxygen’ . Breathing pure oxygen at three atmospheres gen-

erates a fifteenfold increase in dissolved oxygen. This is

sufficiently high to meet the requirements for basal oxy-

genation of tissue in the absence of hemoglobin-borne

oxygen5. Hyperoxygenation also helps to drive oxygen

across partial barriers’7 such as the intracellular and inter-

stitial edema that is associated with compartment syndrome.

The administration of hyperbaric oxygen causes va-

soconstriction by direct action of the increased partial pres-

sure of oxygen on the blood vessels, reducing blood flow

by approximately 20 per cent3. This vasoconstrictive effect

may seem undesirable; however, the net effect is mainte-

nance of oxygenation of the tissues, reduced capillary blood

pressure, and decreased transudation and diapedesis3’5. De-

creased capillary blood pressure causes a shift in the trans-

capillary flow of fluid to promote greater resorption of

extravascular fluid and decreased interstitial-fluid pressure,

thus improving local microcirculation ‘�.

There are two general forms of shock associated with

trauma. The shock that is associated with massive damage

to tissue alters vascular permeability, resulting in intracel-

lular and diffuse protein-rich interstitial edema. Failure of

multiple organs is likely to occur�. The shock that is as-

sociated with soft-tissue injury (as in our model) rarely

precipitates organ-failure syndromes and is primarily as-

sociated with the shift of fluid from interstitial to intra-

cellular spaces2#{176}.The pathophysiology of acute compart-

ment syndrome includes intracellular or interstitial edema,

or both, depending on the etiology, resulting in compromise

of the microcirculation9. When shock and compartment syn-

drome occur concomitantly in the clinical setting, the de-

crease in blood pressure and shifts in fluid decrease the

microcirculatory perfusion in the compartment and increase

the intracompartmental pressure. These factors combine to

lower the threshold of intracompartmental pressure for the

development of ischemia and necrosis. For this reason, im-

proper application or prolonged use of military anti-shock

trousers for the treatment of acute hypovolemia may cause

a compartment syndrome in the lower extremity even in the

absence of injury to the extremity622.

Clinical experience has indicated that there are three

main untoward effects of treatment with hyperbaric

oxygen’2. They are, in order of importance, cerebral oxygen

toxicity, barotrauma to the middle ear, and anxiety due to

confinement within the chamber. These effects are virtually

eliminated by the use of oxygen pressures below the thresh-

old for seizures, appropriate pre-treatment evaluation, and

1224 M. J. SKYHAR ET AL.

judicious use ofproper medications’2. Untoward side effects have trauma to a single extremity, both without and with

of hyperbaric oxygen were not a problem in this study in concomitant hypovolemic shock, followed by appropriate

animals. resuscitation with fluid. The results to date have been en-

The efficacy and indications for the use of hyperbaric couraging. However, hyperbaric chambers are not widely

oxygen in the treatment of patients who have so-called bor- available, and their use in treating patients with compart-

derline compartment syndrome (twenty to fifty millimeters ment syndrome must still be considered adjunctive in nature.

of mercury without a neurological deficit) are presently un-

der investigation at the University of California at San NOTE: The authors thank B. R. Thompson. K. Freestone, R. C. OHara. A. Crenshaw, and. . . . . . . C. Johansson for their expert technical assistance. They also thank J. Robison for her assistance

Diego. This randomized clinical study includes patients who w�#{252}�tie preparation of the manuscript.

References

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